JP3585238B2 - 真核細胞における部位特異的突然変異誘発のための化合物および方法 - Google Patents

真核細胞における部位特異的突然変異誘発のための化合物および方法 Download PDF

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JP3585238B2
JP3585238B2 JP51636795A JP51636795A JP3585238B2 JP 3585238 B2 JP3585238 B2 JP 3585238B2 JP 51636795 A JP51636795 A JP 51636795A JP 51636795 A JP51636795 A JP 51636795A JP 3585238 B2 JP3585238 B2 JP 3585238B2
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Description

1. 発明の分野
本発明は、分子遺伝学の分野に関するものである。特に、本発明は、生存している培養真核細胞に特定の遺伝的変異を導入するための核酸化合物ならびにその使用方法に関する。より詳細には、本発明は、二本鎖核酸の１本の鎖の一部が2'−Ｏまたは2'−OMeリボースを含むヌクレオチドからなり、残りの部分がデオキシリボースヌクレオチドからなる、実質的にワトソン・クリック型塩基対を形成した二本鎖核酸に関する。
2.発明の背景
2.1. キメラおよび／またはハイブリッド二本鎖核酸
本発明の分野は核酸に関するものである。核酸はヘテロポリマー、すなわち、配向されたホスホジエステル結合またはその誘導体によってポリマーへと連結されている、同一でないサブユニットのポリマーである。二本鎖核酸とは、ウラシルまたはチミンに対してはアデニン、シトシンに対してはグアニンという塩基対の法則に従って、二本鎖の第一鎖の各塩基が二本鎖の第二鎖の塩基に対応している核酸のことである。こうした対応（correspondence）を有する逆平行二本鎖はワトソン・クリック型対合（Watson−Crick pairing）をしていると言われる。二本鎖核酸には主に２つのタイプがあり、リボ核酸とデオキシリボ核酸である。それぞれのリボヌクレオチドには同様のデオキシリボヌクレオチドがあり、例えば、アデノシンとデオキシアデノシン、シチジンとデオキシシチジン、グアノシンとデオキシグアノシン、ウリジンとチミジンである。この分野において、リボヌクレオチドとデオキシリボヌクレオチドの両方が同一の鎖に存在している核酸は混合またはキメラ（以後「キメラ」と言う）核酸と称される。デオキシリボヌクレオチドとリボヌクレオチドが互いに対応している二本鎖核酸はハイブリッド二本鎖と呼ばれる。２本の鎖がそれらの塩基の一部において二本鎖核酸の領域を形成している場合、生ずる分子はヘテロ二本鎖と称される。
たいていの場合、二本鎖核酸の２本の鎖は共有結合しておらず、ワトソン・クリック型対合によってのみ結びついている。しかしながら、二本鎖の２本の鎖をオリゴヌクレオチドにより連結させて一本鎖ポリマーを形成することができる。リンキングオリゴヌクレオチドはワトソン・クリック型塩基対を形成しない。第一鎖と第二鎖が一本鎖ポリマーの一部であるヘテロ二本鎖は「ヘアピン二本鎖」または「ステム・ループ（stem and loop）」構造と呼ばれる。以後、前者の用語を用いることにする。
ここで用いるキメリズム（chimerism）は核酸ポリマーの特性であり、そしてハイブリディズム（hybridism）は二本鎖の特性である。例えば、mRNAとその鋳型はどちらもキメラではないがハイブリッド二本鎖を形成し、一方、例えば、キメラオクタヌクレオチド5'd（TTTT）−ｒ（CCCC）3'および5'r（GGGG）−ｄ（AAAA）3'は互いとワトソン・クリック型二本鎖を形成するであろうが、得られる二本鎖はハイブリッド二本鎖ではない。ハイブリッド二本鎖ではない二本鎖核酸を以後「ホモ二本鎖」と呼ぶことにする。特にことわらないかぎり、ホモ二本鎖核酸はデオキシヌクレオチド含有二本鎖のことである。なお、当業者はワトソン・クリック型二本鎖の形成を「ハイブリダイゼーション（ハイブリッド形成）」と呼んでいるが、その場合でさえハイブリッド二本鎖核酸は存在しないことに注意されたい。
Ｘ線回折および二次元NMRによるキメラおよび／またはハイブリッド二本鎖核酸の構造の研究に関心のある人達は、彼らの研究に使用するためのキメラ核酸およびハイブリッド二本鎖核酸を合成してきた。例えば、Salazar,M.ら,1994,J.Mol.Biol.241:440−55およびEgli,M.ら,1993,Biochemistry 32:3221−37（r3d7・d10型のキメラハイブリッド二本鎖）;Ban,C.ら,1994,J.Mol.Biol.236;275−85（d5r1d4型の自己相補的キメラハイブリッド二本鎖）;Chou,S.H.,1991,Biochemistry 30:5248−57（d4r4d4型の自己相補および非自己相補キメラハイブリッド二本鎖）を参照のこと。これらの二本鎖核酸の相補鎖は互いに共有結合で結びついているのではなく、ワトソン・クリック型対合によってのみ結びついていた。
キメラ核酸を合成した第二グループの科学者達は、リボザイム、すなわち自己開裂性であるかまたは他のRNAを開裂するRNA分子、の研究および使用に関心のある人達であった。Perreault,J.P.ら,1990,Nature 344:565;Taylor,N.R.ら,1992,Nucleic Acids Research 20:4559−65;Shimaya T.,1993,Nucleic Acids Research 21:2605を参照のこと。これらの研究者らは、キメラリボザイムが活性であって、しかもRNAリボザイムよりもヌクレアーゼ消化に対して抵抗することを見いだした。キメラリボザイムは自己相補的であり、つまり、ワトソン・クリック型対合鎖が共有結合で結びついている。キメラリボザイムの研究に際して合成された化合物は、キメラリボザイムが安定したハイブリッド二本鎖を含まないという点で、構造研究のために合成され使用された上記のハイブリッド二本鎖分子とは相違している。こうして、DNA結合アームを有するキメラリボザイムがその基質に結合してハイブリッド二本鎖を形成する。Yang,J.H.ら.1990,Biochemistry 29:11156−60を参照のこと。また、Sawata,S.ら,1993,Nucleic Acids Research 21:5656−60;Hendry,P.ら,1992,Nucleic Acids Research 20:5737−41;Shimayama,T.ら,1993,Nucleic Acids Research 21:2605も参照のこと。リボザイムはRNA基質の開裂を触媒し、それゆえハイブリッド二本鎖が溶解される。
2.2. 真核細胞における部位特異的遺伝的変異
分子生物学の分野に習熟した人達は、多くの場合に、単に新しいポリ核酸配列（すなわち、新しい遺伝子）を標的真核細胞の中に導入するのではなく、むしろ標的細胞中の特定の既存遺伝子を改変することが望まれていることを認識している。標的細胞は培養下で用いたり、またはトランスジェニック動物を作出するために用いることができる。
培養下の真核細胞にDNAを導入するための様々な技法が開発されている。こうした技法として、リン酸カルシウム沈殿およびDEAE−デキストラン媒介エンドサイトーシス、エレクトロポレーション、リポソーム媒介融合、そして複製能のないウイルスによる形質導入が挙げられる。しかし、このような技法は真核細胞に機能性遺伝子を導入することはできても、特定の既存遺伝子に変化（突然変異）を簡単に導入することはできない。導入後、外因性DNAは、相同的組換えにより特定位置にではなく、非正統的組換え（illegitimate recombination）により細胞ゲノムの不特定位置に隔離される。
現在まで、高等真核細胞、すなわち哺乳動物細胞またはトリ細胞に、特定部位のまたは部位特異的な遺伝的変異（突然変異誘発）を導入するための一般的に満足のゆく方法は存在していない。高等真核細胞においては非常に長い（＞1kb）核酸の導入による相同的組換えが可能であるが、これらの技法には入念な選択技術の使用が必要となる。なんとなれば、高等真核細胞における非正統的組換え率は相同的組換え率を上回るからである。Thomas,K.R.＆ Capecchi,M.R.,1987,Cell 52:503を参照のこと。さらに、Valancius,V.＆ Smithies O.,1991,Mol.Cell.Biol.11:4389（真核細胞における線状化プラスミドとスーパーコイルドプラスミドの相同的組換えの比較）を参照のこと。
部位特異的突然変異誘発を達成するための一つのアプローチは、細胞の中に直接一本鎖オリゴデオキシヌクレオチドを導入することであった。この手法は酵母Saccharomyces cerevisiaeにおいて成功裏に採用され、酵母では相同的組換えが高等真核細胞中よりも著しく活発に起こった。Moerschell,R.P.ら,1988,Proc.Natl.Acad.Sci.85:524−28;Yamamoto,T.ら,1992,Yeast 8:935−48を参照のこと。しかし、今日まで、一本鎖オリゴヌクレオチドを用いた哺乳動物細胞またはトリ細胞の形質転換が成功したという報告は皆無である。
標的DNAの構造と哺乳動物における相同的組換え率との関係は、交互のプリンおよびピリミジン塩基の領域、すなわち［ｄ（TG）30・ｄ（AC）30］が組換え率を表すということを示した研究によって推論し得る。これらの成果は培養哺乳動物細胞中の非複製プラスミドの研究において実証された。Wahls,W.P.ら,1990,Mol.Cell.Biol.10:785−93を参照のこと。こうした実験が外因性核酸と細胞ゲノムとの組換えを明らかにするまで拡張されることはなかった。
大腸菌において相同的組換えを促進するタンパク質RecAを用いて真核細胞での相同的組換えを促進させようとする試みがなされた。しかし、こうした試みは明らかに成功しなかった。例えば、W.Bertlingの米国特許第4,950,599号には、真核細胞中でRecAを用いても部位特異的突然変異率が極端に低いこと、そして相同的組換え率が向上しないことが記載されている。D.Zarling ＆ E.Senaの特許公開WO 93/22443およびD.C.Gruenert ＆ K.Kunzelmannの公開WO 94/04032は両方とも嚢胞性繊維症に関係した培養細胞系の遺伝的欠陥を修正することを記述している。これらの刊行物は主として操作方法に関するデータよりもむしろ原理を照明する実験データを載せている。こうして、核に接近させてポリヌクレオチド/RecA複合体を導入するために、ZarlingおよびGruenertは膜透過性にした細胞を利用しているが、こうした細胞は増殖能を持ち合わせていない。さらに、RecAにより促進された相同的組換えが無傷の細胞において起こったと主張する場合でさえ、これらの刊行物はその頻度の定量的概算値をまったく提示していない。かくして、原核生物RecAの使用は、生存真核細胞における相同的組換え率が相同的組換えの自然発生率よりも顕著に高いことを納得できる程度に明示していない。
3. 発明の概要
本発明は、デオキシリボヌクレオチドとリボヌクレオチドの両方を含み、対象の遺伝子と相同性の、単一の、共有結合で結びついた二本鎖オリゴヌクレオチドに関する。遺伝的変異を生み出すために、相同領域内に１個またはそれ以上の非対応（以後「異種」または「ミューテーター」と言う）塩基対が存在する。相同的組換えの正常な構成的細胞過程は標的ゲノム部位にミューテーターヌクレオチドを挿入させる。本発明の二本鎖オリゴヌクレオチド（以後「キメラベクター」と言う）は、対象となる遺伝子に異種塩基対を導入することによって該遺伝子を特異的に改変するために用いることができる。異種塩基対は対象の遺伝子と異なる塩基対、または対象の遺伝子に存在するものに加えた塩基対（挿入）であり得、また、異種塩基対は対象の遺伝子中に存在する塩基対の非存在（欠失）であり得る。本発明は、幾分かは、ベクター中に約15〜50塩基対のハイブリッド二本鎖核酸の領域を含めると、対象遺伝子の変異率が非常に増加するという知見に基づいている。異種塩基対の領域が１〜50塩基対である場合、異種塩基対は本発明のベクター中にホモ二本鎖かハイブリッド二本鎖のどちらかとして存在し得る。異種塩基対が50塩基対より長い場合、それらはホモ二本鎖として存在することが好適である。
ベクターは、真核細胞への核酸の導入を可能にする任意の公知方法によって標的細胞の中に導入することができる。理論によって拘束されないが、キメラベクターは、標的細胞の組換え／修復機構によって取り込まれ、遺伝子変換または相同的組換えにより標的遺伝子を変化させると考えられる。
【図面の簡単な説明】
図１は、２つのキメラベクターの模式図を示す。符号の説明は次のとおりである。1:第一鎖、2:第二鎖、3:異種領域、4:相同領域、5:リンカー、6:連結部位。
Figure 0003585238
図1Aは、Ｒ−Ｄ−Ｒ型の連結されたキメラベクターである。
図1Bは、単一の3'および5'末端をもつＲ−Ｄ−Ｒ型のヘアピンキメラベクターである。
5. 発明の詳細な説明
5.1. 本発明のキメラベクターの説明
本発明は、デオキシリボース含有塩基とリボース含有塩基の両方を含む二本鎖核酸を意図している。それらはDNAとRNAの両領域を含み、それゆえ「キメラベクター」と称される。キメラベクターのリボヌクレオチドの2'−Ｏはメチル化され得る。また、ホスホジエステルはどれもホスホロチオジエステルまたはメチホスホノジエステルで置換することができる。
本発明のキメラベクターは単一の核酸ポリマーである。従って、本発明のキメラベクターはワトソン・クリック型塩基対を形成していない少なくとも１塩基、通常は３または４塩基、の少なくとも１つの領域を含まねばならない。これらの不対領域はワトソン・クリック型塩基対の２本の鎖の間のリンカーとして利用される。不対ヌクレオチド領域を有する合成された他のキメラヌクレオチドと対照的に、キメラベクターは酵素活性がない。すなわち、それらは化学反応を触媒しないか、または、それら自体がATPのような生物学的エネルギー源の非存在下で化学反応を受ける。
好ましい実施態様では、リンカーの塩基はデオキシリボヌクレオチドである。ポリマーの3'および5'末端が相補鎖の隣接ヌクレオチドにワトソン・クリック型塩基対合されるように、２つのリンカーをもつキメラベクターを構築することができる。その後、それらは、キメラベクターが単一の連続した環状核酸ポリマーを形成するように連結させることができる。
キメラベクターの残っている実質的に全部の塩基はワトソン・クリック型塩基対を形成する。ここで用いる「塩基がワトソン・クリック型対合する」または「それらが二本鎖核酸を形成する」という記述は、適当な温度および塩条件下でそれらが塩基対または二本鎖核酸を形成しうることを意味すると理解すべきである。いくつかの低塩および／または高温条件下では、ワトソン・クリック型塩基対が熱力学的に安定であることをやめて、二本鎖核酸が融解または変性を起こしうると理解すべきである。また、１個または２個の塩基対ミスマッチは本発明の操作可能性に影響を及ぼさないことを認識すべきである。
本発明キメラベクターは、標的遺伝子に変化（突然変異）を特異的に導入することを目的としたものである。変換の遺伝子部位は、標的部位の配列と同じ（相同である）配列（以後、相同領域と言う）をもつようにキメラベクターの一部を選択することによって決定される。キメラベクター配列と標的遺伝子の間で異なる領域は異種領域と称される。キメラベクターは標的遺伝子に対して異種であるが、ベクターのこの領域においてヘテロ二本鎖でないことに注意されたい。本発明の好ましい実施態様によれば、各キメラベクターには介在異種領域に隣接する２つの相同領域が存在し、これら３つの領域はすべて単一の連続した二本鎖核酸中に存在する。さらに、本発明によれば、各相同領域はハイブリッド二本鎖核酸の部分を含んでいる。ハイブリッド二本鎖の部分は少なくとも４塩基対、好ましくは８塩基対、より好ましくは約20〜30塩基対でありうる。キメラベクターの機能は、3'および5'末端の互いへの連結を可能にするように配置された、ハイブリッド二本鎖の領域内のホモ二本鎖のジヌクレオチド塩基対によって影響されることはない。２つの相同領域の合計の鎖長は少なくとも20塩基対、好ましくは40〜60塩基対でありうる。
本発明によると、ホモ二本鎖核酸の領域はベクターのハイブリッド二本鎖／相同領域の間に配置することができる。介在するホモ二本鎖は異種領域を含むことができる。異種領域が約50塩基対以下、好ましくは約20塩基対以下である場合には、ホモ二本鎖領域の介在は任意である。異種領域が約20塩基対を越える場合は、異種領域を含むホモ二本鎖を介在させることが好適である。
5.2. 本発明のキメラベクターの構築
本発明のキメラベクターは任意の方法で合成することができる。キメラベクターの最も簡便な合成法は、固相DNA合成で用いる技法の変法によるものである。Caruthers,M.H.,1985,Science 230:281−85;Itakura,K.ら,1984,Ann.Rev/Biochem.53:523−56を参照のこと。RNAおよびキメラ核酸の合成を可能にする変法は、Scaringe,S.A.ら,1990,Nucleic Acids Research 18:5433−41;Usman,N.ら,1992,Nucleic Acids Research 20:6695−99;およびSwiderski,P.M.ら,1994,Anal.Biochem 216:83−88に記述されており、これらの全体を参考としてここに組み入れるものとする。キメラ核酸の合成に関する最近の進展は、Usman,N.＆ Cedergren,R.,1992,Trends Bioch.Sci.17:334−９に概説されている。
２つのハイブリッド二本鎖領域間にホモ二本鎖領域が介在したキメラベクターは半合成法を使って構築することができる。ヘアピンコンホメーションを有する２つの合成キメラポリ核酸を構築すべきである。２つの異なる制限酵素消化産物のオーバーラップに相補的なオーバーラップ付着末端をもつ、２つのキメラ核酸の遊離5'および3'末端を構築する。相補的な制限酵素消化末端をもつホモ二本鎖領域を用意する。クローン化DNA断片の両末端への制限酵素部位の付加は当業者によく理解された技法を用いて行うことができ、例えば、限定するものではないが、伸長プライマーを用いるPCR増幅または制限部位を含むリンカーの平滑末端連結がある。２つのキメラヌクレオチドとホモ二本鎖領域は通常の酵素法により連結させることができる。キメラオリゴヌクレオチドが両末端で連結された産物は、非変性条件下でTrisホウ酸EDTA緩衝液にて６％ポリアクリルアミドゲル中で電気泳動を行うことにより、不完全に反応した基質から分離することができる。線状のキャップされた分子は拘束されて、これらの条件下ではより遅く泳動する。
本発明においては自然界に存在するヌクレオチドのみを含むキメラベクターを使用することができる。約20リボヌクレオチドのハイブリッド二本鎖領域を含むキメラベクターは、in vitroでRNase Hに耐性であることが判明した。酵素分解に対する耐性は、リボヌクレオチドを2'−Ｏメチル化リボヌクレオチドで置換することによっても得られる。加えてまたは別途、核酸のホスホジエステル結合をホスホロチオジエステルで置換してもよい。Shimayama,T.ら,1993,Nucleic Acids Research 21:2605を参照のこと。アラビノース含有ヌクレオチドも使用できる。ここで用いる「核酸」という用語は、こうした修飾核酸を包含するものである。
5.3. 本発明のキメラベクターの使用
本発明のキメラベクターは、標的細胞のゲノムの特定位置に突然変異を起こさせるために使用される。標的細胞のゲノムの特定位置はその核酸配列（以後、標的配列と言う）によって定められる。本発明によると、ハイブリッド二本鎖のいくつかの領域の存在を別にすれば、相同領域が標的配列と同一であるキメラベクターが構築される。導入しようとする変化は異種領域によってコードされる。この変化は該配列の１個以上の塩基の変化または１個以上の塩基の付加でありうる。標的配列の変化が約20個以下の塩基の付加である場合、本発明はハイブリッド二本鎖の１つまたは２つの領域を使って実施できる。標的配列の変化が約50個以上の塩基の付加である場合は、異種領域をホモ二本鎖領域内に含ませることが好ましい。
本発明を実施するには、キメラベクターを標的細胞の核の中に導入することが必要である。こうした導入を起こさせる方法はどれも使用できる。かかる方法として、エレクトロポレーション、DEAE−デキストラン、リン酸カルシウム沈殿、リポソーム媒介融合（リポフェクション）、そして直接注入が挙げられる。エレクトロポレーションが特に適している。
本発明の一実施態様において、キメラベクターはトランスジェニック動物を作出するために用いられる。Brinster,R.L.ら,1989,Proc.Natl.Acad.Sci.86:7087に記載の方法に従って、卵の前核にキメラベクターを導入することができる。さらに、T.E.WagnerおよびP.C.Hoppeの米国特許第4,873,191号を参照のこと。上記文献の内容をそのままここに参考として組み入れるものとする。別法として、キメラベクターを胚性幹細胞に導入し、その胚性幹細胞と正常な芽細胞との凝集によってもキメラ動物を作ることができる。トランスジェニック動物は、Capecchi,M.R.,1989,Science 244:1288（その全体を参考としてここに組み入れる）に記載の方法に従って、キメラ動物の子孫として得ることができる。
エレクトロポレーションを用いると、10,000個の処理細胞につき１個程度の細胞が標的配列で特異的に突然変異を起こす（以後「形質転換された」と言う）。かくして、本発明の実施には、突然変異を起こしていない大多数の細胞の中から形質転換された細胞を選別する方法の使用が含まれる。一実施態様において、細胞の形質転換は生育に有利な性質を付与する。生育に有利な性質の非限定的な例として、薬剤耐性、生育調節の変更および代謝産物利用能の変更が挙げられる。別の実施態様では、選別方法としてネガティブ選別を用いる。この方法では、形質転換された細胞が選別条件下で増殖できなくなり、一方、非形質転換細胞は増殖中の細胞を選択的に破壊する条件にさらすことにより除かれる。
また、形質転換細胞は免疫蛍光で検出しうる細胞表面抗原の改変された表現型をもつことができ、この場合は蛍光活性化セルソーター（Fluorescence Activated Cell Sorter）を使って選別することができる。
トランスジェニック動物を前核注入により作出する場合のように、細胞の中にキメラベクターを導入する方法が直接注入である場合は、形質転換率が細胞10,000個につき１個より多くなる。その結果、選別の必要性がかなり軽減される。
一般に、キメラベクターの有効量はエレクトロポレーションで形質転換しようとする培養細胞100万個あたりキメラベクター10〜1000ngの範囲である。
6. 実施例
6.1. 実施例1:Ustilago菌におけるin vivo活性
野生型のUstilagoは機能性ura−３遺伝子（その産物はウラシル生合成経路の一部をなす）をもっている。野生型Ustilagoを5'−fluororotic acid（5FOA）培地で生育させると、細胞はウラシル生合成経路へのこの酸の取込みのために死滅する。ura−３遺伝子に突然変異が起こってura−3 mRNAが産生されなくなると、5FOA培地上でも細胞は生き残る。
内因性ura−３遺伝子の配列は当技術分野で知られている。一組の実験において、この配列の塩基358をチミジンからアデニンに変えた。この変異は機能不全タンパク質をもたらす。
キメラベクターを次のように合成した：
塩基358で突然変異を起こさせるためのベクター（358 RNAベクター）：
Figure 0003585238
358ベクターはヘアピンコンホメーションをとる。下線部分の塩基はリボ核酸残基を示す。太字はミューテーター（異種領域）を示す。イタリック体で記した「Ｔ」は不対合塩基を示す。
対照として使用するために、同一の配列をもつがリボ核酸を含まないベクターも構築した。このベクターではウラシルの代わりにチミジンが用いられた。
塩基358で突然変異を起こさせるための対照ベクター（DNA 358ベクター）
Figure 0003585238
このベクターもヘアピンコンホメーションをとる。この場合も太字の残基がミューテーターである。
in vivo形質転換実験を行うにあたり、当技術分野で公知の方法に従ってU.maydis細胞（107個）から50μｌ形質転換緩衝液中106個の回収率でプロトプラストを作り、異なる量のキメラベクターまたは均質（DNAのみ）ベクターをプロトプラストと37℃で混合してトランスフェクトした。次に細胞を選択培地にまき、生存コロニー（形質転換体）の数を数えた。結果を以下の表に示す。
Figure 0003585238
これらのデータは、RNA358ベクターによる細胞のトランスフェクションが対応するDNAベクターを用いたトランスフェクションよりも大幅に細胞の生存を高めることを示している。
6.2. NIH 3T3細胞の形質転換
NIH 3T3細胞は良性の（制御できる）増殖特性を有するヒト細胞である。悪性の（制御できない）増殖特性は、Gly12をThrで置き換えるがん遺伝子Ｈ−rasの単一の点突然変異によって付与される。かくして、突然変異Ｇ→T12は容易に選択可能な増殖特性の変化を生じさせる。Taparowsky,E.ら,1982,Nature 300:762;Sukumar S.ら,1983,Nature 306:658を参照のこと。
Ｇ→T12突然変異を誘導するために、次の配列を有するキメラベクターを構築した：
Figure 0003585238
この配列は通常の一文字表記で表してある。更なる特徴として、RNAには下線が引いてあり、不対合塩基はイタリック体で、そしてミューテーター塩基は太字で示してある。環化後、キメラベクターは２つのトリチミジニル配列によって実質的に相補的な２つの鎖に分割され、そしてリボース含有ヌクレオチドはすべてこれら２つの鎖の一方にのみ存在することに注目されたい。
2'−OMeリボース塩基を用いて、４個のデオキシリボース残基に隣接する１つ（Ｒ）および２つ（Ｒ−Ｄ−Ｒ）のハイブリッド二本鎖領域をそれぞれ有する２つの型のキメラベクターを合成した。Ｒ−Ｄ−Ｒ型は上記の配列番号３に示され、Ｒ型は塩基６−９（CGAC）がデオキシヌクレオチドであったこと以外は同一である。5'および3'末端はデオキシヌクレオチドであることに注目されたい。組換えDNA法で用いるものと同じDNAリガーゼ法を用いて合成後のキメラベクターを環化させた。連結後、環化したキメラベクターをD600ゲル（AT Biochem,Malvern,PA）中での分離用電気泳動を２回繰り返すことにより基質から単離した。
対照のベクターは次のものであった:1）ハイブリッド二本鎖を欠いている同一の配列（データを示した、「ホモ二本鎖」）;2）配列5'−GCCCACACCGACGGCGCCACCAC−3'（配列番号４）を有する不対合DNA（データを示した、「sDNA」）;3）異種領域を含まない、それゆえミューテーターヌクレオチドを含まないキメラベクター（データを示さず）。
この実験はエレクトロポレーション法を使ってNIH 3T3細胞（１×106個）を形質転換することにより実施した。エレクトロポレーション後、細胞を４×103個/cm2の密度でまき、14日間培養した。フォーカス形成細胞をクリスタルバイオレットで染色して形質転換体を視覚化した。陽性対照として、H rasのT12型をコードするプラスミドpT24を用いた。この対照を用いて、トランスフェクトされたNIH 3T3細胞中における非正統的組換えレベルを測定した。実験を５回繰り返し、その結果を以下の表に要約して示す。以下に示した結果に加えて、ミューテーターコドンを含まないキメラベクターを使用した対照実験では、NIH 3T3細胞の形質転換フォーカスが全く現れなかった。
Figure 0003585238
これらの結果から、キメラベクターは相同的組換えにより特定の突然変異を導入して哺乳動物細胞を形質転換したことがわかる。この実験での形質転換率は、全突然変異Ｈ−ras遺伝子を含むpT24陽性対照ベクターを用いたトランスフェクションにおいて観察された非正統的組換えによる形質転換率よりも高かった。かくして、キメラベクターを用いることにより、非正統的組換え率よりも高い、哺乳動物細胞での相同的組換え率が達成されたことになる。
配列表
配列番号:1
配列の長さ:37塩基対
配列の型：核酸
鎖の数：自己相補的（self complementary）
トポロジー：直鎖状
配列の種類:DNA/RNA
配列の特徴：
特徴を表す記号：−
存在位置:19..32
他の情報:/ラベル＝ａ
／注＝“RNA"
配列
Figure 0003585238
配列番号:2
配列の長さ:37塩基対
配列の型：核酸
鎖の数：自己相補的
トポロジー：直鎖状
配列の種類:DNA
配列
Figure 0003585238
配列番号:3
配列の長さ:53塩基対
配列の型：核酸
鎖の数：自己相補的
トポロジー：直鎖状
配列の種類:DNA/RNA
配列の特徴：
特徴を表す記号：−
存在位置:2..5
他の情報:/ラベル＝ｂ
／注＝“RNA"
配列の特徴：
特徴を表す記号：−
存在位置:10..21
他の情報:/ラベル＝ｄ
／注＝“RNA"
配列の特徴：
特徴を表す記号：−
存在位置:51..52
他の情報:/ラベル＝ｆ
／注＝“RNA"
配列
Figure 0003585238
配列番号:4
配列の長さ:23塩基対
配列の型：核酸
鎖の数：自己相補的
トポロジー：直鎖状
配列の種類:DNA
配列
Figure 0003585238

Claims (4)

  1. 多くても１つの3'末端と１つの5'末端をもつキメラ核酸であって、
    a.不対領域が前記の核酸を第一鎖と第二鎖に分離するように配置されている、連続した不対塩基の領域；
    b.第一鎖の塩基が第二鎖の塩基に対応している、鎖長が少なくとも15塩基対のワトソン・クリック型塩基対を形成した核酸の領域；
    を含んでなり、その際、
    （ｉ）第一鎖は2'−Ｏまたは2'−OMeリボースで構成された連続した少なくとも３ヌクレオチドの領域を含み、これらのヌクレオチドがハイブリッド二本鎖としてワトソン・クリック型塩基対を形成しており、
    （ii）ワトソン・クリック型塩基対を形成した核酸の領 域は、標的遺伝子配列に相同な２つの領域を含み、これ ら２つの相同領域がハイブリッド二本鎖の部分を含み、 これらの相同領域の間には標的遺伝子配列に変異を引き 起こす配列を含む異種領域が介在している、
    ことを特徴とするキメラ核酸。
  2. 第一鎖が２つのハイブリッド二本鎖領域を形成する2'−Ｏまたは2'−OMeリボースで構成された連続ヌクレオチドの２つの領域を含み、各ハイブリッド二本鎖領域は少なくとも４塩基対の長さであり、そして少なくとも１塩基対のホモ二本鎖の介在領域が２つのハイブリッド二本鎖領域間に配置されており、前記のホモ二 本鎖の介在領域が異種領域を含む、請求項１に記載のキメラ核酸。
  3. 核をもつ細胞または細胞集団のゲノムの標的配列に所定の変異を導入する方法であって、
    a.標的配列に相同な２つの領域と、それらの間に配置された、前記の変異をコードする異種領域と、を含む請求項１または２に記載のキメラ核酸を用意し、
    b.該キメラ核酸を該細胞の核内に維持して、該キメラ核 酸と前記の標的配列が遺伝的組換えを起こすようにする、
    ことを含んでなる方法。
  4. 非ヒトトランスジェニック動物の作製に用いるための、請求項１または２に記載のキメラ核酸。
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Families Citing this family (793)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6475795B1 (en) * 1991-07-03 2002-11-05 Meditech Research, Ltd. Use of hyaluronan in gene therapy
US6335434B1 (en) 1998-06-16 2002-01-01 Isis Pharmaceuticals, Inc., Nucleosidic and non-nucleosidic folate conjugates
US8153602B1 (en) 1991-11-19 2012-04-10 Isis Pharmaceuticals, Inc. Composition and methods for the pulmonary delivery of nucleic acids
US20020108136A1 (en) * 1997-03-21 2002-08-08 Sri Transgenic animals produced by homologous sequence targeting
US5523389A (en) * 1992-09-29 1996-06-04 Isis Pharmaceuticals, Inc. Inhibitors of human immunodeficiency virus
AU679566B2 (en) 1993-09-03 1997-07-03 Isis Pharmaceuticals, Inc. Amine-derivatized nucleosides and oligonucleosides
US6420549B1 (en) 1995-06-06 2002-07-16 Isis Pharmaceuticals, Inc. Oligonucleotide analogs having modified dimers
US5731181A (en) * 1996-06-17 1998-03-24 Thomas Jefferson University Chimeric mutational vectors having non-natural nucleotides
US5760012A (en) * 1996-05-01 1998-06-02 Thomas Jefferson University Methods and compounds for curing diseases caused by mutations
US9096636B2 (en) * 1996-06-06 2015-08-04 Isis Pharmaceuticals, Inc. Chimeric oligomeric compounds and their use in gene modulation
US7812149B2 (en) 1996-06-06 2010-10-12 Isis Pharmaceuticals, Inc. 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations
US5898031A (en) 1996-06-06 1999-04-27 Isis Pharmaceuticals, Inc. Oligoribonucleotides for cleaving RNA
US20030044941A1 (en) 1996-06-06 2003-03-06 Crooke Stanley T. Human RNase III and compositions and uses thereof
ATE264864T1 (de) * 1997-03-03 2004-05-15 Applera Corp Verbesserte chimäre oligonukleotidvektoren
US5948653A (en) 1997-03-21 1999-09-07 Pati; Sushma Sequence alterations using homologous recombination
US6524613B1 (en) 1997-04-30 2003-02-25 Regents Of The University Of Minnesota Hepatocellular chimeraplasty
GB9711015D0 (en) * 1997-05-28 1997-07-23 Zeneca Ltd Improvements in or relating to organic compounds
ATE321882T1 (de) 1997-07-01 2006-04-15 Isis Pharmaceuticals Inc Zusammensetzungen und verfahren zur verabreichung von oligonukleotiden über die speiseröhre
CN100419083C (zh) * 1997-08-05 2008-09-17 金默拉根有限公司 用混合双链寡核苷酸在植物中实现定点遗传改变的用途
US7102055B1 (en) * 1997-11-18 2006-09-05 Pioneer Hi-Bred International, Inc. Compositions and methods for the targeted insertion of a nucleotide sequence of interest into the genome of a plant
NZ503859A (en) * 1997-11-18 2003-02-28 Pioneer Hi Bred Int Non-identical minimal recombination sites (FRT) which are non-identical for targeted integration of nucleotide sequences into transformed plants
CA2309719A1 (en) 1997-11-18 1999-05-27 Pioneer Hi-Bred International, Inc. Targeted manipulation of genes in plants
EP0945507A1 (de) * 1998-03-27 1999-09-29 Boehringer Mannheim Gmbh Tumorspezifische Expressionskontrollregion und deren Verwendung
US20040186071A1 (en) 1998-04-13 2004-09-23 Bennett C. Frank Antisense modulation of CD40 expression
US6004804A (en) * 1998-05-12 1999-12-21 Kimeragen, Inc. Non-chimeric mutational vectors
US6010907A (en) 1998-05-12 2000-01-04 Kimeragen, Inc. Eukaryotic use of non-chimeric mutational vectors
EP1080103A4 (en) * 1998-05-21 2003-07-02 Isis Pharmaceuticals Inc COMPOSITIONS AND METHODS FOR NON-PARENTERAL ADMINISTRATION OF OLIGONUCLEOTIDES
CA2329252A1 (en) 1998-05-21 1999-11-25 Isis Pharmaceuticals Inc. Compositions and methods for topical delivery of oligonucleotides
US6693185B2 (en) 1998-07-17 2004-02-17 Bayer Bioscience N.V. Methods and means to modulate programmed cell death in eukaryotic cells
DE19836098A1 (de) 1998-07-31 2000-02-03 Hoechst Schering Agrevo Gmbh Pflanzen, die eine modifizierte Stärke synthetisieren, Verfahren zur Herstellung der Pflanzen, ihre Verwendung sowie die modifizierte Stärke
CA2344653A1 (en) 1998-09-29 2000-04-06 Gamida Cell Ltd. Methods of controlling proliferation and differentiation of stem and progenitor cells
US6077709A (en) 1998-09-29 2000-06-20 Isis Pharmaceuticals Inc. Antisense modulation of Survivin expression
AU773808B2 (en) 1998-11-09 2004-06-10 Bayer Cropscience Aktiengesellschaft Nucleic acid molecules from rice and their use for the production of modified starch
US6438561B1 (en) * 1998-11-19 2002-08-20 Navigation Technologies Corp. Method and system for using real-time traffic broadcasts with navigation systems
US6917882B2 (en) 1999-01-19 2005-07-12 Maxygen, Inc. Methods for making character strings, polynucleotides and polypeptides having desired characteristics
US6376246B1 (en) 1999-02-05 2002-04-23 Maxygen, Inc. Oligonucleotide mediated nucleic acid recombination
WO2000042559A1 (en) * 1999-01-18 2000-07-20 Maxygen, Inc. Methods of populating data structures for use in evolutionary simulations
US20030054390A1 (en) * 1999-01-19 2003-03-20 Maxygen, Inc. Oligonucleotide mediated nucleic acid recombination
US6368861B1 (en) 1999-01-19 2002-04-09 Maxygen, Inc. Oligonucleotide mediated nucleic acid recombination
US7024312B1 (en) 1999-01-19 2006-04-04 Maxygen, Inc. Methods for making character strings, polynucleotides and polypeptides having desired characteristics
US6961664B2 (en) 1999-01-19 2005-11-01 Maxygen Methods of populating data structures for use in evolutionary simulations
DE60044223D1 (de) 1999-01-19 2010-06-02 Maxygen Inc Durch oligonukleotide-vermittelte nukleinsäuren-rekombination
US20070065838A1 (en) * 1999-01-19 2007-03-22 Maxygen, Inc. Oligonucleotide mediated nucleic acid recombination
US6127124A (en) * 1999-01-20 2000-10-03 Isis Pharmaceuticals, Inc. Fluorescence based nuclease assay
US7098192B2 (en) 1999-04-08 2006-08-29 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of STAT3 expression
CA2368655A1 (en) * 1999-04-08 2000-10-19 Gregory M. Glenn Dry formulation for transcutaneous immunization
CA2370132C (en) 1999-05-07 2012-01-24 E. I. Du Pont De Nemours And Company Auxin transport proteins
US6656730B1 (en) 1999-06-15 2003-12-02 Isis Pharmaceuticals, Inc. Oligonucleotides conjugated to protein-binding drugs
US6271360B1 (en) 1999-08-27 2001-08-07 Valigen (Us), Inc. Single-stranded oligodeoxynucleotide mutational vectors
CA2389441A1 (en) 1999-10-07 2001-04-12 Valigen, Inc. Compositions and methods for plant genetic modification
AR025996A1 (es) 1999-10-07 2002-12-26 Valigen Us Inc Plantas no transgenicas resistentes a los herbicidas.
US7430477B2 (en) 1999-10-12 2008-09-30 Maxygen, Inc. Methods of populating data structures for use in evolutionary simulations
US20030190644A1 (en) 1999-10-13 2003-10-09 Andreas Braun Methods for generating databases and databases for identifying polymorphic genetic markers
US7414170B2 (en) * 1999-11-19 2008-08-19 Kirin Beer Kabushiki Kaisha Transgenic bovines capable of human antibody production
US7820878B2 (en) * 1999-11-19 2010-10-26 Kyowa Hakko Kirin Co., Ltd. Production of ungulates, preferably bovines that produce human immunoglobulins
AU1777301A (en) * 1999-11-19 2001-05-30 Hematech, Llc Production of ungulates, preferably bovines that produce human immunoglobulins
US7074983B2 (en) * 1999-11-19 2006-07-11 Kirin Beer Kabushiki Kaisha Transgenic bovine comprising human immunoglobulin loci and producing human immunoglobulin
US20020055479A1 (en) 2000-01-18 2002-05-09 Cowsert Lex M. Antisense modulation of PTP1B expression
US6261840B1 (en) 2000-01-18 2001-07-17 Isis Pharmaceuticals, Inc. Antisense modulation of PTP1B expression
US20060134629A1 (en) * 2000-03-20 2006-06-22 Link Charles J Methods and compositions for elucidating protein expression profiles in cells
US6897020B2 (en) * 2000-03-20 2005-05-24 Newlink Genetics Inc. Methods and compositions for elucidating relative protein expression levels in cells
OA12240A (en) * 2000-03-27 2006-05-10 Univ Delaware Targeted chromosomal genomic alterations with modified single stranded oligonucleotides.
US6936467B2 (en) * 2000-03-27 2005-08-30 University Of Delaware Targeted chromosomal genomic alterations with modified single stranded oligonucleotides
WO2001087914A2 (en) * 2000-05-17 2001-11-22 University Of Delaware Plant gene targeting using oligonucleotides
US6686188B2 (en) * 2000-05-26 2004-02-03 Amersham Plc Polynucleotide encoding a human myosin-like polypeptide expressed predominantly in heart and muscle
US6656700B2 (en) * 2000-05-26 2003-12-02 Amersham Plc Isoforms of human pregnancy-associated protein-E
WO2001094610A2 (en) * 2000-06-05 2001-12-13 Thomas Jefferson University Binary hybrid mutational vectors
US7468475B2 (en) 2000-06-16 2008-12-23 Schmuelling Thomas Method for modifying plant morphology, biochemistry and physiology
US6958214B2 (en) 2000-07-10 2005-10-25 Sequenom, Inc. Polymorphic kinase anchor proteins and nucleic acids encoding the same
CA2417344A1 (en) * 2000-07-27 2002-02-07 University Of Delaware Methods for enhancing targeted gene alteration using oligonucleotides
US6875907B2 (en) 2000-09-13 2005-04-05 Pioneer Hi-Bred International, Inc. Antimicrobial peptides and methods of use
US20020119570A1 (en) * 2000-09-25 2002-08-29 Kyonggeun Yoon Targeted gene correction by single-stranded oligodeoxynucleotides
US20020123474A1 (en) * 2000-10-04 2002-09-05 Shannon Mark E. Human GTP-Rho binding protein2
US7560622B2 (en) 2000-10-06 2009-07-14 Pioneer Hi-Bred International, Inc. Methods and compositions relating to the generation of partially transgenic organisms
US7491534B2 (en) 2000-12-22 2009-02-17 Kirin Holdings Kabushiki Kaisha Methods for altering cell fate to generate T-cells specific for an antigen of interest
US20020142397A1 (en) * 2000-12-22 2002-10-03 Philippe Collas Methods for altering cell fate
AU2002232858B2 (en) * 2000-12-22 2007-01-11 Sab, Llc Methods for cloning mammals using reprogrammed donor chromatin or donor cells
WO2002059337A1 (en) * 2001-01-26 2002-08-01 Georgetown University School Of Medicine Anti-apoptopic gene scc-s2 and diagnostic and therapeutic uses thereof
AU2002303176A1 (en) * 2001-03-27 2002-10-15 University Of Delaware Genomics applications for modified oligonucleotides
AU2002303261A1 (en) * 2001-04-06 2002-10-21 Georgetown University Gene brcc2 and diagnostic and therapeutic uses thereof
WO2002081642A2 (en) 2001-04-06 2002-10-17 Georgetown University Gene brcc-3 and diagnostic and therapeutic uses thereof
AU2002305151A1 (en) * 2001-04-06 2002-10-21 Georgetown University Gene scc-112 and diagnostic and therapeutic uses thereof
WO2002081640A2 (en) * 2001-04-06 2002-10-17 Georgetown University Gene shinc-1 and diagnostic and therapeutic uses thereof
US20030045830A1 (en) * 2001-04-17 2003-03-06 De Bizemont Therese Gene therapy with chimeric oligonucleotides delivered by a method comprising a step of iontophoresis
US20040063922A1 (en) * 2001-04-17 2004-04-01 Conrad Charles A. Methods and compositions for catalytic DNA exchange in a sequence specific manner
US7053195B1 (en) 2001-06-12 2006-05-30 Syngenta Participatious Ag Locked nucleic acid containing heteropolymers and related methods
US20030148408A1 (en) 2001-09-18 2003-08-07 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
US7803915B2 (en) 2001-06-20 2010-09-28 Genentech, Inc. Antibody compositions for the diagnosis and treatment of tumor
KR100576674B1 (ko) 2001-06-20 2006-05-10 제넨테크, 인크. 종양의 진단 및 치료를 위한 방법 및 이를 위한 조성물
WO2003000707A2 (en) 2001-06-21 2003-01-03 Isis Pharmaceuticals, Inc. Antisense modulation of superoxide dismutase 1, soluble expression
EP1925672A1 (en) 2001-06-22 2008-05-28 Syngeta Participations AG Abiotic stress responsive polynucleotides and polypeptides
US7425545B2 (en) 2001-07-25 2008-09-16 Isis Pharmaceuticals, Inc. Modulation of C-reactive protein expression
US6964950B2 (en) 2001-07-25 2005-11-15 Isis Pharmaceuticals, Inc. Antisense modulation of C-reactive protein expression
US20030096772A1 (en) 2001-07-30 2003-05-22 Crooke Rosanne M. Antisense modulation of acyl CoA cholesterol acyltransferase-2 expression
US7407943B2 (en) 2001-08-01 2008-08-05 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein B expression
AU2002326589B2 (en) * 2001-08-07 2008-06-05 University Of Delaware Compositions and methods for the prevention and treatment of Huntington's disease
US7227014B2 (en) 2001-08-07 2007-06-05 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein (a) expression
US20030084473A1 (en) * 2001-08-09 2003-05-01 Valigen Non-transgenic herbicide resistant plants
US7456335B2 (en) * 2001-09-03 2008-11-25 Basf Plant Science Gmbh Nucleic acid sequences and their use in methods for achieving pathogen resistance in plants
EP1427856B1 (en) 2001-09-18 2011-05-11 Carnegie Institution Of Washington Fusion proteins useful for detecting analytes
WO2003027264A2 (en) * 2001-09-27 2003-04-03 University Of Delaware Coisogenic eukaryotic cell collections
MXPA04002817A (es) 2001-09-27 2004-07-05 Pioneer Hi Bred Int Polinucleotidos de fitato y metodos de uso.
AU2002341905A2 (en) * 2001-09-27 2003-04-07 University Of Delaware Composition and methods for enhancing oligonucleotide-directed nucleic acid sequence alteration
US7468244B2 (en) * 2001-09-27 2008-12-23 University Of Delaware Polymorphism detection and separation
NZ566396A (en) 2001-10-09 2009-07-31 Isis Pharmaceuticals Inc Antisense modulation of insulin-like growth factor binding protein 5 expressions
US6750019B2 (en) 2001-10-09 2004-06-15 Isis Pharmaceuticals, Inc. Antisense modulation of insulin-like growth factor binding protein 5 expression
US6965025B2 (en) 2001-12-10 2005-11-15 Isis Pharmaceuticals, Inc. Antisense modulation of connective tissue growth factor expression
KR100801388B1 (ko) 2002-01-02 2008-02-05 제넨테크, 인크. 종양의 진단 및 치료 방법 및 이를 위한 조성물
IL152904A0 (en) 2002-01-24 2003-06-24 Gamida Cell Ltd Utilization of retinoid and vitamin d receptor antagonists for expansion of renewable stem cell populations
WO2003062404A1 (en) 2002-01-25 2003-07-31 Gamida-Cell Ltd. Methods of expanding stem and progenitor cells and expanded cell populations obtained thereby
WO2003064621A2 (en) 2002-02-01 2003-08-07 Ambion, Inc. HIGH POTENCY siRNAS FOR REDUCING THE EXPRESSION OF TARGET GENES
US20060009409A1 (en) 2002-02-01 2006-01-12 Woolf Tod M Double-stranded oligonucleotides
ATE508188T1 (de) 2002-02-01 2011-05-15 Life Technologies Corp Oligonukleotid-zusammensetzungen mit verbesserter wirksamkeit
US7135326B2 (en) * 2002-02-07 2006-11-14 E. I. Du Pont De Nemours And Company UDP-glucosyltransferases
WO2003069984A2 (en) 2002-02-20 2003-08-28 American Integrated Biologics, Inc. Transgenic production in saliva
US7566535B2 (en) * 2002-03-07 2009-07-28 University Of Delaware Enhanced oligonucleotide-mediated nucleic acid sequence alteration
AU2003233489B2 (en) 2002-04-08 2008-10-02 Pioneer Hi-Bred International, Inc. Enhanced silk exsertion under stress
US7244565B2 (en) * 2002-04-10 2007-07-17 Georgetown University Gene shinc-3 and diagnostic and therapeutic uses thereof
US7138512B2 (en) * 2002-04-10 2006-11-21 Georgetown University Gene SHINC-2 and diagnostic and therapeutic uses thereof
MXPA04010092A (es) 2002-04-16 2004-12-13 Genentech Inc Composiciones y metodos para el diagnostico y tratamiento de tumores.
WO2003093296A2 (en) 2002-05-03 2003-11-13 Sequenom, Inc. Kinase anchor protein muteins, peptides thereof, and related methods
CN1653174A (zh) 2002-05-08 2005-08-10 巴斯福植物科学有限公司 用于提高植物含油量的方法
US20030228317A1 (en) * 2002-05-22 2003-12-11 Prafulla Gokhale Gene BRCC-1 and diagnostic and therapeutic uses thereof
US7199107B2 (en) 2002-05-23 2007-04-03 Isis Pharmaceuticals, Inc. Antisense modulation of kinesin-like 1 expression
US20030228558A1 (en) * 2002-06-11 2003-12-11 Bloom William Dennis Method of training brokers in a multi-level marketing business
US20050221326A1 (en) * 2002-06-12 2005-10-06 Avi Orr-Urtreger Oligonucleotides antibodies and kits including same for treating prostate cancer and determining predisposition thereto
US20060258602A1 (en) * 2002-09-20 2006-11-16 Yukio Ando Site-specific gene conversion promoter and gene therapeutic
AU2003278957A1 (en) 2002-09-26 2004-04-23 Amgen, Inc. Modulation of forkhead box o1a expression
AU2003282477A1 (en) * 2002-10-07 2004-05-04 Napro Bio Therapeutics, Inc. Methods and compositions for reducing screening in oligonucleotide-directed nucleic acid sequence alteration
US9150606B2 (en) 2002-11-05 2015-10-06 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2'-modified nucleosides for use in gene modulation
EP1560839A4 (en) 2002-11-05 2008-04-23 Isis Pharmaceuticals Inc CHIMERIC OLIGOMER COMPOUNDS AND THEIR USE IN GENE MODULATION
US9150605B2 (en) * 2002-11-05 2015-10-06 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2′-modified nucleosides for use in gene modulation
AU2003291755A1 (en) 2002-11-05 2004-06-07 Isis Pharmaceuticals, Inc. Oligomers comprising modified bases for binding cytosine and uracil or thymine and their use
BR0315300A (pt) * 2002-11-08 2005-08-30 Hematech Llc Ungulados transgênicos tendo atividade de proteìna priÈnica reduzida e seus usos
EP1569695B1 (en) 2002-11-13 2013-05-15 Genzyme Corporation Antisense modulation of apolipoprotein b expression
ES2417879T3 (es) 2002-11-13 2013-08-09 Genzyme Corporation Modulación antisentido de la expresión de la apolipoproteína B
EP1572971B1 (en) 2002-11-15 2009-09-30 Morphotek Inc. Methods of generating high-production of antibodies from hybridomas created by in vitro immunization
US7144999B2 (en) 2002-11-23 2006-12-05 Isis Pharmaceuticals, Inc. Modulation of hypoxia-inducible factor 1 alpha expression
PT1578973E (pt) 2002-12-19 2008-10-16 Bayer Cropscience Ag Células de plantas e plantas que sintetizam um amido com uma melhor viscosidade final
NZ541637A (en) 2003-02-11 2008-07-31 Antisense Therapeutics Pty Ltd Modulation of insulin like growth factor I receptor
WO2004074440A2 (en) 2003-02-17 2004-09-02 Metanomics Gmbh Preparation of organisms with faster growth and/or higher yield
US7803781B2 (en) 2003-02-28 2010-09-28 Isis Pharmaceuticals, Inc. Modulation of growth hormone receptor expression and insulin-like growth factor expression
US20040185559A1 (en) 2003-03-21 2004-09-23 Isis Pharmaceuticals Inc. Modulation of diacylglycerol acyltransferase 1 expression
EP1613746B1 (de) 2003-03-31 2013-03-06 University Of Bristol Neue pflanzliche acyltransferasen spezifisch für langkettige, mehrfach ungesättigte fettsäuren
US20040205840A1 (en) * 2003-04-11 2004-10-14 Pioneer Hi-Bred International, Inc. Method for reducing gene expression
ATE514781T1 (de) 2003-04-15 2011-07-15 Basf Plant Science Gmbh Nukleinsäuresequenzen, die für proteine in zusammenhang mit abiotischer stressreaktion kodieren, sowie pflanzenzellen und pflanzen mit erhöhter umweltstressverträglichkeit
WO2005014828A2 (en) 2003-08-01 2005-02-17 Basf Plant Science Gmbh Process for the production of fine chemicals in plants
US7598227B2 (en) 2003-04-16 2009-10-06 Isis Pharmaceuticals Inc. Modulation of apolipoprotein C-III expression
US7399853B2 (en) 2003-04-28 2008-07-15 Isis Pharmaceuticals Modulation of glucagon receptor expression
CA2524495A1 (en) 2003-06-03 2005-01-13 Eli Lilly And Company Modulation of survivin expression
US7790691B2 (en) * 2003-06-20 2010-09-07 Isis Pharmaceuticals, Inc. Double stranded compositions comprising a 3′-endo modified strand for use in gene modulation
CA2533701A1 (en) 2003-07-31 2005-02-17 Isis Pharmaceuticals, Inc. Oligomeric compounds and compositions for use in modulation of small non-coding rnas
EP2166090B1 (de) 2003-08-01 2015-07-01 BASF Plant Science GmbH Verfahren zur Herstellung mehrfach ungesättigter Fettsäuren in transgenen Organismen
PT1654276E (pt) 2003-08-11 2013-03-25 Kweek En Researchbed Agrico Bv Plantas resistentes a fungos e seus usos
US7825235B2 (en) 2003-08-18 2010-11-02 Isis Pharmaceuticals, Inc. Modulation of diacylglycerol acyltransferase 2 expression
US20050053981A1 (en) 2003-09-09 2005-03-10 Swayze Eric E. Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini
PE20050469A1 (es) 2003-09-18 2005-09-10 Lilly Co Eli Modulacion de la expresion de eif4e
WO2005027962A1 (en) 2003-09-18 2005-03-31 Isis Pharmaceuticals, Inc. 4’-thionucleosides and oligomeric compounds
DK1678194T3 (da) 2003-10-10 2013-10-07 Alchemia Oncology Pty Ltd Modulering af syntese og degradering af hyaluronan i behandlingen af sygdom
EP2305798A3 (en) 2003-10-23 2011-04-20 Illumigen Biosciences, Inc. Detection of mutations in a gene associated with resistance to viral infection, OAS1
US20050191653A1 (en) 2003-11-03 2005-09-01 Freier Susan M. Modulation of SGLT2 expression
PT2161283E (pt) 2003-11-17 2014-08-29 Genentech Inc Composições que compreendem anticorpos contra cd79b conjugados a um agente de inibição do crescimento ou agente citotóxico e métodos para o tratamento de tumor de origem hematopoiética
US20050120397A1 (en) * 2003-11-24 2005-06-02 Hermann Steller Compounds and methods for regulation of spermatid differentiation
MXPA06006998A (es) 2003-12-17 2007-04-17 Cropdesign Nv Plantas que tienen caracteristicas de crecimiento modificadas y metodo para producir las mismas.
WO2005062923A2 (en) * 2003-12-24 2005-07-14 Massachusetts Institute Of Technology Gene targets for enhanced carotenoid production
US7741070B2 (en) 2003-12-24 2010-06-22 Massachusetts Institute Of Technology Gene targets for enhanced carotenoid production
US7608699B2 (en) * 2003-12-29 2009-10-27 Rockefeller University Synthetic nuclear localization signal derived from lentiviral integrase and methods of use thereof
JP2007520222A (ja) 2004-01-20 2007-07-26 アイシス ファーマシューティカルズ インコーポレイテッド グルココルチコイドレセプター発現の調節
US7468431B2 (en) 2004-01-22 2008-12-23 Isis Pharmaceuticals, Inc. Modulation of eIF4E-BP2 expression
CA2799245C (en) 2004-02-25 2016-08-30 Pioneer Hi-Bred International, Inc. Novel bacillus thuringiensis crystal polypeptides, polynucleotides, and compositions thereof
EP3543324B1 (de) 2004-02-27 2022-11-30 BASF Plant Science GmbH Verfahren zur herstellung mehrfach ungesättigten fettsäuren in transgenen pflanzen
CA2558726C (en) 2004-02-27 2017-11-07 Basf Plant Science Gmbh Method for producing unsaturated .omega.-3-fatty acids in transgenic organisms
US8569474B2 (en) 2004-03-09 2013-10-29 Isis Pharmaceuticals, Inc. Double stranded constructs comprising one or more short strands hybridized to a longer strand
US8790919B2 (en) * 2004-03-15 2014-07-29 Isis Pharmaceuticals, Inc. Compositions and methods for optimizing cleavage of RNA by RNase H
US8314226B2 (en) * 2004-03-29 2012-11-20 The General Hospital Corporation Oligonucleotide complex compositions and methods of use as gene alteration tools
US20050244869A1 (en) 2004-04-05 2005-11-03 Brown-Driver Vickie L Modulation of transthyretin expression
EP2540734B1 (en) 2004-04-05 2016-03-30 Alnylam Pharmaceuticals, Inc. Process and reagents for oligonucleotide synthesis and purification
US7420099B2 (en) * 2004-04-22 2008-09-02 Kirin Holdings Kabushiki Kaisha Transgenic animals and uses thereof
US20070072815A1 (en) * 2004-05-04 2007-03-29 Kmiec Eric B Methods and kits to increase the efficiency of oligonucleotide-directed nucleic acid sequence alteration
US7825293B2 (en) 2004-05-28 2010-11-02 Cropdesign N.V. Plants having improved growth characteristics and a method for making the same
US8394947B2 (en) 2004-06-03 2013-03-12 Isis Pharmaceuticals, Inc. Positionally modified siRNA constructs
CA2735315A1 (en) 2004-06-09 2005-12-29 Pioneer Hi-Bred International, Inc. Plastid transit peptides
WO2007087815A2 (en) 2004-12-17 2007-08-09 Metanomics Gmbh Process for the control of production of fine chemicals
WO2006069610A2 (en) 2004-07-02 2006-07-06 Metanomics Gmbh Process for the production of fine chemicals
US8680062B2 (en) 2004-07-06 2014-03-25 Deliversir Ltd. System for delivering therapeutic agents into living cells and cells nuclei
US7928288B2 (en) 2004-07-12 2011-04-19 Cropdesign N.V. Plants having improved growth characteristics and method for making the same
ES2430827T3 (es) 2004-07-31 2013-11-21 Metanomics Gmbh Preparación de organismos con crecimiento más rápido y/o rendimiento más alto
PT2409713E (pt) 2004-08-10 2015-10-09 Genzyme Corp Oligonucleótidos para utilização em modulação dos níveis de lipoproteínas e colesterol em humanos
EP1778845A2 (en) 2004-08-16 2007-05-02 CropDesign N.V. Plants having improved growth characteristics and method for making the same
US7884086B2 (en) 2004-09-08 2011-02-08 Isis Pharmaceuticals, Inc. Conjugates for use in hepatocyte free uptake assays
EP1799812A4 (en) 2004-09-16 2009-09-09 Gamida Cell Ltd EX VIVO CULTIVATION METHODS OF STEM CELLS AND PRECURSOR BY CO-CULTURE WITH MESENCHYMAL CELLS
AU2005286738A1 (en) 2004-09-17 2006-03-30 Isis Pharmaceuticals, Inc. Enhanced antisense oligonucleotides
AU2005286428B2 (en) 2004-09-24 2012-08-23 Basf Plant Science Gmbh Nucleic acid sequences encoding proteins associated with abiotic stress response and plant cells and plants with increased tolerance to environmental stress
US8765700B2 (en) 2004-10-20 2014-07-01 Antisense Therapeutics Ltd. Topical administrations of antisense compounds to VLA-4 for the treatment of respiratory conditions
US20080108502A1 (en) 2004-10-29 2008-05-08 Cropdesign N.V. Plants Having Improved Growth Characteristics And Method For Making The Same
AR051866A1 (es) 2004-12-24 2007-02-14 Cropdesign Nv Plantas con aumento del rendimiento y metodo de prepracion
WO2006071219A1 (en) 2004-12-28 2006-07-06 Pioneer Hi-Bred International, Inc. Improved grain quality through altered expression of seed proteins
CN101111600A (zh) 2005-01-27 2008-01-23 克罗普迪塞恩股份有限公司 产率增加的植物及其制备方法
EP1851317B1 (en) 2005-02-23 2011-10-26 North Carolina State University Alteration of tobacco alkaloid content through modification of specific cytochrome p450 genes
EP1871883A1 (en) 2005-03-02 2008-01-02 Metanomics GmbH Process for the production of fine chemicals
US20140199313A1 (en) 2005-03-02 2014-07-17 Metanomics Gmbh Process for the Production of Fine Chemicals
WO2006094976A2 (en) 2005-03-08 2006-09-14 Basf Plant Science Gmbh Expression enhancing intron sequences
MX2007010922A (es) 2005-03-10 2007-10-12 Genentech Inc Metodos y composiciones para modular la integridad vascular.
DE102005013779A1 (de) 2005-03-22 2006-09-28 Basf Plant Science Gmbh Verfahren zur Herstellung von mehrfach ungesättigten C20- und C22-Fettsäuren mit mindestens vier Doppelbindungen in transgenen Pflanzen
EP1707632A1 (de) 2005-04-01 2006-10-04 Bayer CropScience GmbH Phosphorylierte waxy-Kartoffelstärke
EP1874936B1 (en) 2005-04-19 2013-10-30 BASF Plant Science GmbH Improved methods controlling gene expression
WO2006113666A2 (en) 2005-04-19 2006-10-26 Massachusetts Institute Of Technology Amphiphilic polymers and methods of use thereof
US20070011752A1 (en) * 2005-05-06 2007-01-11 American Integrated Biologics, Inc. Production of human proteins in transgenic animal saliva
EP2261362A3 (en) 2005-05-25 2011-04-20 Pioneer Hi-Bred International Inc. Methods for improving crop plant architecture and yield
WO2007008300A2 (en) 2005-05-31 2007-01-18 ECOLE POLYTECHNIQUE FéDéRALE DE LAUSANNE Triblock copolymers for cytoplasmic delivery of gene-based drugs
WO2006138145A1 (en) 2005-06-14 2006-12-28 Northwestern University Nucleic acid functionalized nanoparticles for therapeutic applications
BRPI0612671A2 (pt) 2005-06-23 2010-11-30 Basf Plant Science Gmbh métodos melhorados para a produção de plantas férteis zea mays (milho) estavelmente transformadas
US8119858B2 (en) 2005-07-06 2012-02-21 Cropdesign N.V. Plant yield improvement by Ste20-like gene expression
DE102005038036A1 (de) 2005-08-09 2007-02-15 Basf Plant Science Gmbh Verfahren zur Herstellung von Arachidonsäure und/oder Eicosapentaensäure in transgenen Nutzpflanzen
EP1915452A2 (en) 2005-08-12 2008-04-30 BASF Plant Science GmbH Nucleic acid sequences encoding proteins associated with abiotic stress response and plant cells and plants with increased tolerance to environmental stress
US7842856B2 (en) 2005-08-25 2010-11-30 The Board Of Trustees Of The University Of Illinois Herbicide resistance gene, compositions and methods
EP1931788A2 (en) 2005-09-15 2008-06-18 CropDesign N.V. Plants having increased yield and method for making the same
EP1931789B1 (en) 2005-09-20 2016-05-04 BASF Plant Science GmbH Methods for controlling gene expression using ta-siran
GB2431158A (en) 2005-10-13 2007-04-18 Rothamsted Res Ltd Process for the production of arachidonic and/or eicosapentaenoic acid
US8853492B2 (en) 2005-11-07 2014-10-07 Cropdesign N.V. Plants having improved growth characteristics and a method for making the same
WO2007051866A2 (en) 2005-11-07 2007-05-10 Cropdesign N.V. Plants having improved growth characteristics and a method for making the same
CA2628505A1 (en) 2005-11-08 2007-05-18 Basf Plant Science Gmbh Use of armadillo repeat (arm1) polynucleotides for obtaining resistance to pathogens in plants
AU2006311005B2 (en) 2005-11-08 2013-06-06 Cropdesign N.V. Plants having improved growth characteristics and a method for making the same
AU2006315788A1 (en) 2005-11-10 2007-05-24 Pioneer Hi-Bred International, Inc. Dof (DNA binding with one finger) sequences and methods of use
US20070199096A1 (en) 2005-11-14 2007-08-23 E.I. Du Pont De Nemours And Company Compositions and Methods for Altering Alpha- and Beta-Tocotrienol Content
CA2630602A1 (en) 2005-11-21 2007-05-31 Isis Pharmaceuticals, Inc. Modulation of eif4e-bp2 expression
US7723574B2 (en) 2005-11-24 2010-05-25 Basf Plant Science Gmbh Process for the production of Δ5-unsaturated fatty acids in transgenic organisms
EP1957034A2 (de) * 2005-11-24 2008-08-20 Basf Se Chimäre keratinbindende effektorproteine
US8846393B2 (en) 2005-11-29 2014-09-30 Gamida-Cell Ltd. Methods of improving stem cell homing and engraftment
EP2157172A3 (en) 2005-12-01 2010-03-24 CropDesign N.V. Plants having improved growth characteristics and methods for making the same
US20090105341A1 (en) 2005-12-24 2009-04-23 Teagasc Dairy Products Research Centre Process for the production of trans-10, cis 12 octadecadienoic acid
EP1976567B1 (en) 2005-12-28 2020-05-13 The Scripps Research Institute Natural antisense and non-coding rna transcripts as drug targets
US7592505B2 (en) 2005-12-30 2009-09-22 Pioneer Hi-Bred International, Inc. UDP-xylose synthases (UXS) polynucleotides, polypeptides, and uses thereof
EP1979484B1 (en) 2006-01-12 2014-03-19 BASF Plant Science GmbH Use of stomatin (stm1) polynucleotides for achieving a pathogen resistance in plants
EP2465341B1 (en) 2006-01-12 2014-12-17 Cibus Europe B.V. EPSPS Mutants
JP5425474B2 (ja) 2006-01-26 2014-02-26 アイシス ファーマシューティカルズ， インコーポレーテッド ハンチンチン対する、組成物及びその使用
PL1984381T3 (pl) 2006-01-27 2011-03-31 Isis Pharmaceuticals Inc Zmodyfikowane w pozycji 6 analogi bicykliczne kwasów nukleinowych
US7569686B1 (en) 2006-01-27 2009-08-04 Isis Pharmaceuticals, Inc. Compounds and methods for synthesis of bicyclic nucleic acid analogs
US8129515B2 (en) 2006-01-27 2012-03-06 Isis Pharmaceuticals, Inc. Oligomeric compounds and compositions for the use in modulation of microRNAs
CA2895745A1 (en) 2006-02-09 2007-08-16 Pioneer Hi-Bred International, Inc. Genes for enhancing nitrogen utilization efficiency in crop plants
GB0603160D0 (en) 2006-02-16 2006-03-29 Rothamsted Res Ltd Nucleic acid
EP2343376A3 (en) 2006-03-24 2011-11-23 BASF Plant Science GmbH Proteins associated with abiotic stress response and homologs
CA2638978A1 (en) 2006-03-31 2007-10-11 Basf Plant Science Gmbh Plants having enhanced yield-related traits and a method for making the same
AU2007299219A1 (en) 2006-04-05 2008-03-27 Metanomics Gmbh Process for the production of a fine chemical
EP2251349A1 (en) 2006-04-19 2010-11-17 Pioneer Hi-Bred International, Inc. Isolated polynucleotide molecules corresponding to mutant and wild-type alleles of the maize D9 gene and methods of use
EP2019692B1 (en) 2006-05-05 2014-06-04 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of gccr
JP5441688B2 (ja) 2006-05-11 2014-03-12 アイシス ファーマシューティカルズ， インコーポレーテッド ５’修飾二環式核酸類似体
US7666854B2 (en) 2006-05-11 2010-02-23 Isis Pharmaceuticals, Inc. Bis-modified bicyclic nucleic acid analogs
EP2441839A1 (en) 2006-05-30 2012-04-18 CropDesign N.V. Plants with reduced expression of REVOLUTA (REV) having enhanced yield-related traits and a method for making the same
CA2651961A1 (en) 2006-05-31 2007-12-06 Metanomics Gmbh Manipulation of the nitrogen metabolism
CA2649341A1 (en) 2006-06-08 2007-12-13 Basf Plant Science Gmbh Plants having improved growth characteristics and method for making the same
EP2599869A3 (en) 2006-06-15 2013-09-11 CropDesign N.V. Plants having enhanced yield-related traits and a method for making the same
CN105087634A (zh) 2006-06-15 2015-11-25 克罗普迪塞恩股份有限公司 具有增强的产量相关性状的nac转录因子受调节表达的植物和用于产生该植物的方法
RU2483057C2 (ru) 2006-06-28 2013-05-27 Ньюселис Инк. Смеси жирных кислот и их применение
US8198253B2 (en) 2006-07-19 2012-06-12 Isis Pharmaceuticals, Inc. Compositions and their uses directed to HBXIP
MX2009001177A (es) 2006-08-02 2009-02-13 Cropdesign Nv Plantas con caracteristicas mejoradas y un metodo para producirlas.
ES2558133T3 (es) 2006-08-02 2016-02-02 Cropdesign N.V. Plantas transformadas con el polipéptido SYT que tienen el rendimiento aumentado en estrés abiótico y procedimiento de producción de las mismas
AU2007291330B2 (en) 2006-08-30 2013-01-17 Basf Plant Science Gmbh Method for increasing resistance to pathogens in transgenic plants
US8454948B2 (en) 2006-09-14 2013-06-04 Medgenics Medical Israel Ltd. Long lasting drug formulations
AU2007294858B2 (en) 2006-09-14 2011-05-12 Medgenics Medical Israel, Ltd Long lasting drug formulations
EP2177605B1 (de) 2006-10-06 2014-12-10 BASF Plant Science GmbH Delta-5 Desaturasen und Verfahren zur Herstellung mehrfach ungesättigter Fettsäuren in transgenen nicht-humanen Organismen
US8329988B2 (en) 2006-10-12 2012-12-11 Basf Plant Science Gmbh Method for increasing pathogen resistance in transgenic plants
CN101589148B (zh) 2006-10-13 2014-07-02 巴斯福植物科学有限公司 产量提高的植物
BRPI0720192A2 (pt) 2006-10-24 2013-12-31 Basf Plant Science Gmbh Método para gerar ou aumentar uma resistência a pelo menos um fungo biotrófico em uma planta ou uma parte de uma planta, seqüência de polipeptídio artificial, seqüência de ácido nucléico artificial, cassete de expressão recombinante, vetor recombinante, e, microorganismo recombinante
WO2008059048A1 (en) 2006-11-16 2008-05-22 Basf Plant Science Gmbh Plants having enhanced yield-related traits and a method for making the same using consensus sequences from the yabby protein family
BRPI0718977A2 (pt) 2006-11-24 2014-02-04 Cropdesign Nv Método para aumentar rendimento de sementes em plantas em relação às plantas de controle, construção, uso da mesma, planta, parte de planta ou célula de planta, método para a produção de uma planta transgênica tendo redimento aumentado de sementes em relação às plantas de controle, planta transgênica, partes colhíveis de uma planta, produtos, e, uso de um ácido nucleico
WO2008071767A1 (en) 2006-12-15 2008-06-19 Cropdesign N.V. Plants having enhanced seed yield-related traits and a method for making the same
EP2395093A3 (en) 2006-12-21 2012-08-01 BASF Plant Science GmbH Plants having enhanced yield-related traits and a method for making the same
EP1935428A1 (en) * 2006-12-22 2008-06-25 Antisense Pharma GmbH Oligonucleotide-polymer conjugates
EP2102364B1 (en) 2006-12-28 2019-01-23 Pioneer Hi-Bred International, Inc. Genetic markers for orobanche resistance in sunflower
AU2007342674B2 (en) * 2007-01-10 2013-09-19 Purdue Research Foundation Polypeptide inhibitors of HSP27 kinase and uses therefor
WO2008087141A2 (en) 2007-01-15 2008-07-24 Basf Plant Science Gmbh Use of subtilisin (rnr9) polynucleotides for achieving a pathogen resistance in plants
CN101627125B (zh) 2007-01-30 2013-05-15 克罗普迪塞恩股份有限公司 具有增强的产量相关性状的植物及其制备方法
CN103233037A (zh) 2007-01-31 2013-08-07 巴斯福植物科学有限公司 具有增强的产量相关性状和/或提高的非生物胁迫抗性的植物和制备该植物的方法
KR101488800B1 (ko) 2007-02-09 2015-02-04 노오쓰웨스턴 유니버시티 세포내 타겟 검출용 입자
MX2009008600A (es) 2007-02-28 2009-08-21 Cropdesign Nv Plantas con rasgos mejorados relacionados con el rendimiento y un metodo para producirlas.
US8153863B2 (en) * 2007-03-23 2012-04-10 New York University Transgenic plants expressing GLK1 and CCA1 having increased nitrogen assimilation capacity
NZ600923A (en) 2007-04-04 2013-10-25 Basf Plant Science Gmbh AHAS mutants
US9156865B2 (en) 2007-04-23 2015-10-13 Deliversir Ltd System for delivering therapeutic agents into living cells and cells nuclei
US9556210B2 (en) 2007-04-23 2017-01-31 Sabag-Rfa Ltd. System for delivering therapeutic agents into living cells and cells nuclei
EP2144633B1 (en) * 2007-04-23 2014-07-16 Deliversir Ltd A system for delivering therapeutic agents into living cells and cells nuclei
EP2069509B1 (en) 2007-05-03 2013-09-18 BASF Plant Science GmbH Plants having enhanced yield-related traits and a method for making the same
AU2008252996B2 (en) 2007-05-22 2014-01-30 Basf Plant Science Gmbh Plants with increased tolerance and/or resistance to environmental stress and increased biomass production
CA2687635A1 (en) 2007-05-22 2008-11-27 Basf Plant Science Gmbh Plant cells and plants with increased tolerance and/or resistance to environmental stress and increased biomass production-ko
EP2172556B1 (en) 2007-05-23 2015-07-22 CropDesign N.V. Plants having enhanced yield-related traits and a method for making the same
EP2152733A2 (en) 2007-05-25 2010-02-17 CropDesign N.V. Yield enhancement in plants by modulation of maize alfins
DK2160464T3 (da) 2007-05-30 2014-08-04 Univ Northwestern Nukleinsyrefunktionaliserede nanopartikler til terapeutiske anvendelser
WO2008150729A2 (en) 2007-05-30 2008-12-11 Isis Pharmaceuticals, Inc. N-substituted-aminomethylene bridged bicyclic nucleic acid analogs
EP2173760B2 (en) 2007-06-08 2015-11-04 Isis Pharmaceuticals, Inc. Carbocyclic bicyclic nucleic acid analogs
EP2508610A1 (en) 2007-06-29 2012-10-10 BASF Plant Science GmbH Plants having enhanced yield-related traits and a method for making the same
EP2176280B2 (en) 2007-07-05 2015-06-24 Isis Pharmaceuticals, Inc. 6-disubstituted bicyclic nucleic acid analogs
CN104404078A (zh) 2007-07-20 2015-03-11 巴斯夫植物科学有限公司 具有增强的产率相关性状的植物及其制备方法
AR067748A1 (es) 2007-07-31 2009-10-21 Basf Plant Science Gmbh Plantas que tienen rasgos mejorados relacionados con el rendimiento y un metodo para obtenerlas
EP2183372A2 (en) 2007-07-31 2010-05-12 BASF Plant Science GmbH Plants having enhanced yield-related traits and a method for making the same
WO2009021137A2 (en) 2007-08-07 2009-02-12 Purdue Research Foundation Kinase inhibitors and uses thereof
WO2009023855A2 (en) 2007-08-15 2009-02-19 Isis Pharmaceuticals, Inc. Tetrahydropyran nucleic acid analogs
US9617557B2 (en) 2007-09-14 2017-04-11 Basf Plant Science Gmbh Plants having increased yield-related traits by expressing a growth-regulating factor (GRF) polypeptide and method for making the same
CN103695459A (zh) 2007-09-18 2014-04-02 巴斯夫植物科学有限公司 产量提高的植物
JP2010538670A (ja) 2007-09-21 2010-12-16 ビーエーエスエフ プラント サイエンス ゲーエムベーハー 増強された収穫高関連形質を有する植物およびその作製方法
CN101939435A (zh) 2007-09-21 2011-01-05 巴斯夫植物科学有限公司 具有增加的产量的植物
WO2009039442A1 (en) 2007-09-21 2009-03-26 California Institute Of Technology Nfia in glial fate determination, glioma therapy and astrocytoma treatment
BR122018070230B1 (pt) 2007-10-05 2023-01-10 Cibus Europe B.V. Método para produção de planta resistente à herbicida
US20100280098A1 (en) * 2007-10-05 2010-11-04 Juliano Rudolph L Receptor targeted oligonucleotides
US20090111099A1 (en) * 2007-10-27 2009-04-30 Yongsheng Ma Promoter Detection and Analysis
US20110071047A1 (en) * 2007-10-27 2011-03-24 O.D. 260 Inc. Promoter detection and analysis
WO2009056566A2 (en) 2007-10-29 2009-05-07 Basf Plant Science Gmbh Plants having enhanced yield-related traits and a method for making the same
WO2009064771A2 (en) 2007-11-12 2009-05-22 North Carolina State University Alteration of tobacco alkaloid content through modification of specific cytochrome p450 genes
EP2219680A2 (en) 2007-11-13 2010-08-25 Isis Pharmaceuticals, Inc. Compounds and methods for modulating protein expression
MX2010005565A (es) 2007-11-20 2010-06-11 Pioneer Hi Bred Int Genes de señalizacion de etileno en maiz y su modulacion para mejor tolerancia al estres en plantas.
USRE47320E1 (en) 2007-11-20 2019-03-26 Ionis Pharmaceuticals, Inc. Modulation of CD40 expression
US8546556B2 (en) * 2007-11-21 2013-10-01 Isis Pharmaceuticals, Inc Carbocyclic alpha-L-bicyclic nucleic acid analogs
US8704043B2 (en) 2007-11-22 2014-04-22 Cropdesign N.V. Plants having increased yield-related traits and a method for making the same
EP2220111A1 (en) 2007-11-26 2010-08-25 BASF Plant Science GmbH Plants having enhanced yield-related traits and a method for making the same
BRPI0821748A2 (pt) * 2007-12-19 2019-09-24 Basf Plant Science Gmbh método para produzir uma planta com rendimento aumentado, molécula isolada de ácido nucleico, construção de ácido nucleico, vetor, processo para produzir um polipeptídeo, polipeptídeo, anticorpo, núcleo de célula de planta, célula de planta, tecido de planta, material de propagação, semente, pólen, progênie, ou uma parte de planta, ou uma planta com rendimento aumento, processo para a indentificação de um composto, método para a produção de uma composição agrícola, composição, polipeptídeo ou molécula de ácido nucleico, uso dos ácidos nucléicos, e, método para a indentificação de uma planta com um rendimento aumentado
CA2708506A1 (en) 2007-12-20 2009-07-02 Basf Plant Science Gmbh Plants having enhanced yield-related traits and a method for making the same
AU2008340002A1 (en) 2007-12-21 2009-07-02 Basf Plant Science Gmbh Plants with increased yield (KO NUE)
ES2653573T3 (es) * 2007-12-27 2018-02-07 Cibus Europe B.V. Mezclas de éster butílico de ácido graso
EP2599875A3 (en) 2008-01-25 2013-07-17 BASF Plant Science GmbH Plants having enhanced yield-related traits and a method for making the same
EP2247733A2 (en) 2008-01-31 2010-11-10 National Institute of Biological Sciences Plants having altered growth and/or development and a method for making the same
WO2009100320A2 (en) 2008-02-07 2009-08-13 Isis Pharmaceuticals, Inc. Bicyclic cyclohexitol nucleic acid analogs
CA2716180A1 (en) 2008-02-27 2009-09-03 Basf Plant Science Gmbh Plants with increased yield
EP2282744B1 (en) 2008-03-21 2018-01-17 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising tricyclic nucleosides and methods for their use
DK2285819T3 (da) 2008-04-04 2013-12-02 Isis Pharmaceuticals Inc Oligomere forbindelser omfattende neutralt bundne, terminale bicykliske nukleosider
EP3029143A1 (en) 2008-04-16 2016-06-08 BASF Plant Science GmbH Plants having enhanced yield-related traits and a method for making the same
AU2009243552A1 (en) 2008-05-05 2009-11-12 Basf Plant Science Gmbh Plants having enhanced yield-related traits and a method for making the same
KR20110023862A (ko) * 2008-05-23 2011-03-08 시부스 오일즈, 엘엘씨 효모를 사용한 스쿠알렌 생산
CA2724993A1 (en) 2008-06-20 2009-12-23 Basf Plant Science Gmbh Plants having enhanced yield-related traits and a method for making the same
EP2975130A3 (en) 2008-06-26 2016-04-20 BASF Plant Science GmbH Plants having enhanced yield-related traits and a method for making the same
CN102143971A (zh) 2008-07-04 2011-08-03 巴斯夫植物科学有限公司 通过过表达编码tfl-1 样蛋白的多核苷酸而具有增强的产量相关性状的植物及其制备方法
WO2010007035A1 (en) 2008-07-17 2010-01-21 Basf Plant Science Gmbh Plants having enhanced yield-related traits and a method for making the same
MX2011000778A (es) 2008-07-31 2011-03-15 Basf Plant Science Gmbh Plantas con caracteristicas modificadas de crecimiento y un metodo para obtenerlas.
EP2324044A4 (en) 2008-08-04 2012-04-25 Univ Miami STING (INTERFERON GENE STIMULATOR), A REGULATOR OF INDIAN IMMUNE RESPONSES
WO2010020654A2 (en) 2008-08-19 2010-02-25 Basf Plant Science Gmbh Plants with increased yield by increasing or generating one or more activities in a plant or a part thereof
MX2011001475A (es) 2008-08-20 2011-03-29 Basf Plant Science Gmbh Plantas que tienen rasgos mejorados relacionados con el rendimiento y un metodo para obtenerlas.
MX2011002143A (es) 2008-08-25 2011-07-20 Excaliard Pharmaceuticals Inc Oligonucleotidos antisentido dirigidos contra el factor de crecimiento del tejido conectivo y usos de los mismos.
CA2737303C (en) 2008-09-11 2019-06-11 Keygene N.V. Method for diagnostic marker development
US20110195843A1 (en) 2008-09-23 2011-08-11 Basf Plant Science Gmbh Plants with Increased Yield (LT)
WO2010036698A1 (en) 2008-09-24 2010-04-01 Isis Pharmaceuticals, Inc. Substituted alpha-l-bicyclic nucleosides
US8604192B2 (en) 2008-09-24 2013-12-10 Isis Pharmaceuticals, Inc. Cyclohexenyl nucleic acids analogs
MX2011002675A (es) 2008-09-24 2011-04-21 Basf Plant Science Gmbh Plantas que tienen rasgos mejorados relacionados con el rendimiento y un metodo para obtenerlas.
AP2011005671A0 (en) 2008-09-26 2011-04-30 Basf Agrochemical Products Bv Herbicide-resistant AHAS-mutants and methods of use.
BRPI0920263B1 (pt) 2008-10-15 2021-09-21 Ionis Pharmaceuticals, Inc Compostos compreendendo um oligonucleotídeo modificado, composição e uso dos mesmos
AU2009322865B2 (en) * 2008-10-20 2013-07-18 Moerae Matrix, Inc. Polypeptide for treating or preventing adhesions
AR075465A1 (es) 2008-10-22 2011-04-06 Basf Se Uso de herbicidas de sulfonilurea en plantas cultivadas
WO2010046422A2 (en) 2008-10-22 2010-04-29 Basf Se Use of auxin type herbicides on cultivated plants
AR073969A1 (es) 2008-10-23 2010-12-15 Basf Plant Science Gmbh Un metodo para producir una celula transgenca con mayor contenido de acido gamma aminobutirico ( gaba)
CN102264907A (zh) 2008-10-23 2011-11-30 巴斯夫植物科学有限公司 产量增加的植物(nue)
WO2010048549A2 (en) 2008-10-24 2010-04-29 Isis Pharmaceuticals, Inc. 5' and 2' bis-substituted nucleosides and oligomeric compounds prepared therefrom
EP2358398A2 (en) 2008-10-24 2011-08-24 Isis Pharmaceuticals, Inc. Oligomeric compounds and methods
WO2010056519A1 (en) 2008-10-30 2010-05-20 Pioneer Hi-Bred International, Inc. Manipulation of glutamine synthetases (gs) to improve nitrogen use efficiency and grain yield in higher plants
EP2184351A1 (en) 2008-10-30 2010-05-12 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Polynucleotides encoding caryophyllene synthase and uses thereof
CA2741973A1 (en) 2008-11-12 2010-05-20 Basf Plant Science Gmbh Plants having enhanced abiotic stress tolerance and/or enhanced yield-related traits and a method for making the same
KR101336213B1 (ko) 2008-11-14 2013-12-05 후지안 후다 바이오테크 코퍼레이션 리미티드 열내성 비 ｋ12 에스체리치아 콜리 피타아제 및 그 제조
US9139827B2 (en) 2008-11-24 2015-09-22 Northwestern University Polyvalent RNA-nanoparticle compositions
EA201170752A1 (ru) 2008-12-03 2012-04-30 Басф Плант Сайенс Гмбх Растения с повышенной устойчивостью к абиотическому стрессу и/или улучшенными характеристиками урожайности и способ их получения
CN108042560A (zh) 2008-12-04 2018-05-18 库尔纳公司 通过抑制针对沉默调节蛋白1的天然反义转录物来治疗沉默调节蛋白1相关的疾病
US8431775B2 (en) 2008-12-04 2013-04-30 Pioneer Hi Bred International Inc Methods and compositions for enhanced yield by targeted expression of knotted1
JP6091752B2 (ja) 2008-12-04 2017-03-08 クルナ・インコーポレーテッド Ｅｐｏに対する天然アンチセンス転写物の抑制によるエリスロポエチン（ｅｐｏ）関連疾患の治療
CN107338251A (zh) 2008-12-04 2017-11-10 库尔纳公司 通过抑制肿瘤抑制基因的天然反义转录物***抑制基因相关性疾病
US9327008B2 (en) 2008-12-10 2016-05-03 Purdue Research Foundation Cell-permeant peptide-based inhibitor of kinases
PL2376638T3 (pl) 2008-12-12 2014-01-31 Basf Plant Science Gmbh Desaturazy oraz sposób wytwarzania wielonienasyconych kwasów tłuszczowych w organizmach transgenicznych
AU2009335740B2 (en) 2008-12-17 2016-04-21 Sarepta Therapeutics, Inc. Antisense compositions and methods for modulating contact hypersensitivity or contact dermatitis
DE112009003749T5 (de) 2008-12-17 2012-11-15 Basf Plant Science Gmbh Pflanzen mit gesteigerten ertragsbezogenen Eigenschaften und/oder gesteigerter abiotischerStresstoleranz und Verfahren zur Herstellung derselben
EP2204086A1 (en) 2009-01-02 2010-07-07 Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung (IPK) Six row-type barley
US20100233270A1 (en) 2009-01-08 2010-09-16 Northwestern University Delivery of Oligonucleotide-Functionalized Nanoparticles
US8653080B2 (en) 2009-01-14 2014-02-18 Salk Institute For Biological Studies Methods for screening and compounds that protect against amyloid diseases
US20110283420A1 (en) 2009-01-28 2011-11-17 Basf Plant Science Company Gmbh Plants having enhanced yield-related traits and a method for making the same
WO2010091308A2 (en) 2009-02-06 2010-08-12 Isis Pharmaceuticals, Inc. Oligomeric compounds and methods
WO2010090969A1 (en) 2009-02-06 2010-08-12 Isis Pharmaceuticals, Inc. Tetrahydropyran nucleic acid analogs
HUE026280T2 (en) 2009-02-12 2016-06-28 Curna Inc Treatment of brain-derived neurotrophic factor (BDNF) -related diseases by inhibition of natural antisense transcripts associated with BDNF \ t
EP2396408B1 (en) 2009-02-12 2017-09-20 CuRNA, Inc. Treatment of glial cell derived neurotrophic factor (gdnf) related diseases by inhibition of natural antisense transcript to gdnf
DE112010000887T5 (de) 2009-02-25 2012-09-27 Basf Plant Science Company Gmbh Pflanzen mit gesteigerten Ertragsmerkmalen und Verfahren zu deren Herstellung
US8716553B2 (en) 2009-03-02 2014-05-06 Pioneer Hi Bred International Inc NAC transcriptional activators involved in abiotic stress tolerance
EP2963116B1 (en) 2009-03-04 2020-11-11 CuRNA, Inc. Treatment of sirtuin 1 (sirt1) related diseases by inhibition of natural antisense transcript to sirt 1
JP6116242B2 (ja) 2009-03-16 2017-04-19 クルナ・インコーポレーテッド 核因子（赤血球由来２）様２（ｎｒｆ２）に対する天然アンチセンス転写物の抑制によるｎｒｆ２関連疾患の治療
JP5904935B2 (ja) 2009-03-17 2016-04-20 クルナ・インコーポレーテッド デルタ様１ホモログ（ｄｌｋ１）に対する天然アンチセンス転写物の抑制によるｄｌｋ１関連疾患の治療
UA108071C2 (uk) 2009-04-14 2015-03-25 Піонер Хай-Бред Інтернешнл, Інк. Спосіб поліпшення витривалості до нестачі азоту у рослини
CA2759100A1 (en) 2009-04-21 2010-10-28 Basf Plant Science Company Gmbh Rna-mediated induction of gene expression in plants
US20120047602A1 (en) 2009-04-21 2012-02-23 Basf Plant Science Company Gmbh RNA-Mediated Induction of Gene Expression in Plants
EP3248618A1 (en) 2009-04-22 2017-11-29 Massachusetts Institute Of Technology Innate immune suppression enables repeated delivery of long rna molecules
KR20150046788A (ko) 2009-04-29 2015-04-30 바스프 플랜트 사이언스 게엠베하 향상된 수확량 관련 형질을 갖는 식물 및 이의 제조 방법
CA2760266A1 (en) 2009-04-29 2010-11-04 Basf Plant Science Company Gmbh Plants having enhanced yield-related traits and a method for making the same
DK2424987T3 (en) 2009-05-01 2018-02-26 Curna Inc TREATMENT OF HEMOGLOBIN (HBF / HBG) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENSE TRANSCRIPTION TO HBF / HBG
MX2011011678A (es) 2009-05-04 2011-12-06 Pioneer Hi Bred Int Mejora de la produccion en plantas mediante la modulacion del factor de transcripcion ap2.
CN103223177B (zh) 2009-05-06 2016-08-10 库尔纳公司 通过针对脂质转运和代谢基因的天然反义转录物的抑制治疗脂质转运和代谢基因相关疾病
US20120096593A1 (en) 2009-05-06 2012-04-19 Yves Hatzfeld Plants Having Enhanced Yield-Related Traits And/Or Enhanced Abiotic Stress Tolerance And A Method For Making The Same
WO2010129746A2 (en) 2009-05-06 2010-11-11 Curna, Inc. Treatment of tristetraproline (ttp) related diseases by inhibition of natural antisense transcript to ttp
EP2432881B1 (en) 2009-05-18 2017-11-15 CuRNA, Inc. Treatment of reprogramming factor related diseases by inhibition of natural antisense transcript to a reprogramming factor
KR101703695B1 (ko) 2009-05-22 2017-02-08 큐알엔에이, 인크. 전사 인자 ｅ3(ｔｆｅ3)에 대한 천연 안티센스 전사체의 억제에 의해 ｔｆｅ3 및 인슐린 수용체 기질 2(ｉｒｓ2)의 치료
KR20120024819A (ko) 2009-05-28 2012-03-14 오피케이오 큐알엔에이, 엘엘씨 항바이러스 유전자에 대한 천연 안티센스 전사체의 억제에 의한 트리스테트라프롤린 관련된 질환의 치료
KR101702689B1 (ko) 2009-06-16 2017-02-06 큐알엔에이, 인크. Ｐｏｎ1에 대한 천연 안티센스 전사체의 억제에 의한 파라옥소나제 1(ｐｏｎ1) 관련된 질환의 치료
ES2620960T3 (es) 2009-06-16 2017-06-30 Curna, Inc. Tratamiento de enfermedades relacionadas con un gen de colágeno mediante la inhibición de un transcrito antisentido natural a un gen de colágeno
US9683023B2 (en) 2009-06-19 2017-06-20 Basf Plant Science Company Gmbh Plants having enhanced yield-related traits and a method for making the same
CA2765889A1 (en) 2009-06-24 2010-12-29 Opko Curna, Llc Treatment of tumor necrosis factor receptor 2 (tnfr2) related diseases by inhibition of natural antisense transcript to tnfr2
KR101807324B1 (ko) 2009-06-26 2017-12-08 큐알엔에이, 인크. 다운 증후군 유전자에 대한 천연 안티센스 전사체의 억제에 의한 다운 증후군 유전자 관련된 질환의 치료
BRPI1008189A2 (pt) 2009-06-30 2015-08-25 Du Pont Planta transgenica semente transgenica obtida a partir da planta transgencia semente transgencia metodo de produção de uma planta transgenica metodo de produção de sementes transgenicas metodo de produto e ou subproduto da semente transgenica e semente transgenica obtida pelo metodo
ES2385451T3 (es) 2009-07-10 2012-07-25 Freie Universität Berlin Rock2 y Rock3, dos nuevas variantes de ganancia de función de los receptores de citoquinina AHK2 y AHK3
EP2275564A1 (en) 2009-07-17 2011-01-19 Freie Universität Berlin Means and method for the production of transgenic plants that are resistant to clubroot
MX2012000928A (es) 2009-07-23 2012-03-29 Basf Plant Science Co Gmbh Plantas con produccion aumentada.
CA2768571A1 (en) 2009-07-24 2011-01-27 Pioneer Hi-Bred International, Inc. The use of dimerization domain component stacks to modulate plant architecture
US9890195B2 (en) * 2009-07-27 2018-02-13 Purdue Research Foundation MK2 inhibitor compositions and methods to enhance neurite outgrowth, neuroprotection, and nerve regeneration
WO2011017492A2 (en) 2009-08-05 2011-02-10 Pioneer Hi-Bred International, Inc. Novel eto1 genes and use of same for reduced ethylene and improved stress tolerance in plants
ES2585360T3 (es) 2009-08-05 2016-10-05 Curna, Inc. Tratamiento de enfermedades relacionadas con un gen de la insulina (INS) por inhibición de la transcripción antisentido natural en un gen de la insulina (INS)
EP2462153B1 (en) 2009-08-06 2015-07-29 Isis Pharmaceuticals, Inc. Bicyclic cyclohexose nucleic acid analogs
GB0914012D0 (en) 2009-08-11 2009-09-16 Plant Bioscience Ltd Stress tolerant plants
BR112012003796A2 (pt) 2009-08-19 2016-11-22 Basf Plant Science Co Gmbh método para intensificar traços relacionados ao rendimento em plantas com relação às plantas de controle, construto, uso de um construto, planta, parte de planta ou célula de planta, método para a produção de uma planta trangênica, partes colhíveis de uma planta, produtos, e, uso de um ácido nucleico.
CN102549149A (zh) 2009-08-20 2012-07-04 先锋国际良种公司 在玉蜀黍中功能性表达酵母硝酸盐转运蛋白(ynt1)以改善硝酸盐吸收
WO2011031482A2 (en) 2009-08-25 2011-03-17 Curna, Inc. Treatment of 'iq motif containing gtpase activating protein' (iqgap) related diseases by inhibition of natural antisense transcript to iqgap
SG178388A1 (en) 2009-08-31 2012-03-29 Basf Plant Science Co Gmbh Regulatory nucleic acid molecules for enhancing seed-specific and/or seed-preferential gene expression in plants
CA2772267A1 (en) 2009-08-31 2011-03-03 Basf Plant Science Company Gmbh Regulatory nucleic acid molecules for enhancing seed-specific gene expression in plants promoting enhanced polyunsaturated fatty acid synthesis
CA3235747A1 (en) 2009-08-31 2011-03-03 Basf Plant Science Company Gmbh Regulatory nucleic acid molecules for enhancing constitutive gene expression in plants
CA2772715C (en) 2009-09-02 2019-03-26 Genentech, Inc. Mutant smoothened and methods of using the same
EP3118320A1 (en) 2009-09-25 2017-01-18 BASF Plant Science Company GmbH Plants having enhanced yield-related traits and a method for making the same
BR112012006616A2 (pt) 2009-09-25 2018-07-10 Basf Plant Science Co Gmbh método para intensificar traços relacionados a rendimento em plantas com relação a plantas de controle, planta ou parte da mesma, construto, uso de um construto, planta. ou parte da planta ou célula de planta transformada com um construto, método para a produção de uma planta transgênica, planta transgênica, partes colhíveis de uma planta, produtos derivados de uma planta, uso de um ácido nucleíco, molécula de ácido nucleíco isolado, polipeptídeo isolado, uso de qualquer um, dois ou mais ácidos nucleícos e método para aprimorar os traços relacionados a rendimento em plantas.
WO2011041796A1 (en) 2009-10-02 2011-04-07 Pioneer Hi-Bred International, Inc. Down-regulation of acc synthase for improved plant performance
WO2011050194A1 (en) 2009-10-22 2011-04-28 Genentech, Inc. Methods and compositions for modulating hepsin activation of macrophage-stimulating protein
CN102666858A (zh) 2009-10-22 2012-09-12 巴斯夫植物科学有限公司 具有增强的产量相关性状的植物和用于产生该植物的方法
US9376690B2 (en) 2009-10-30 2016-06-28 Northwestern University Templated nanoconjugates
AR078829A1 (es) 2009-10-30 2011-12-07 Du Pont Plantas y semillas con niveles alterados de compuesto de almacenamiento, construcciones relacionadas y metodos relacionados con genes que codifican proteinas similares a las aldolasas bacterianas de la clase ii del acido 2,4- dihidroxi-hept-2-eno-1,7-dioico
EP3199634A1 (en) 2009-11-13 2017-08-02 Sarepta Therapeutics, Inc. Antisense antiviral compound and method for treating influenza viral infection
DE112010004383T5 (de) 2009-11-13 2012-08-23 Basf Plant Science Company Gmbh Pflanzen mit gesteigerten Ertragsmerkmalen und Verfahren zu deren Herstellung
WO2011061656A1 (en) 2009-11-17 2011-05-26 Basf Plant Science Company Gmbh Plants with increased yield
DK3219815T3 (da) 2009-11-23 2019-12-16 Cibus Europe Bv Fremgangsmåder og sammensætninger til at fremstille squalen under anvendelse af gær
JP5856065B2 (ja) 2009-11-30 2016-02-09 ジェネンテック， インコーポレイテッド 腫瘍の診断と治療のための組成物と方法
JP6025567B2 (ja) 2009-12-16 2016-11-16 カッパーアールエヌエー，インコーポレイテッド 膜結合転写因子ペプチダーゼ、部位１（ｍｂｔｐｓ１）に対する天然アンチセンス転写物の阻害によるｍｂｔｐｓ１関連性疾患の治療
WO2011079261A2 (en) 2009-12-23 2011-06-30 Curna, Inc. Treatment of hepatocyte growth factor (hgf) related diseases by inhibition of natural antisense transcript to hgf
RU2619185C2 (ru) 2009-12-23 2017-05-12 Курна, Инк. Лечение заболеваний, связанных с разобщающим белком 2 (ucp2), путем ингибирования природного антисмыслового транскрипта к ucp2
US8946514B2 (en) 2009-12-28 2015-02-03 E.I. Du Pont De Nemours And Company Sorghum fertility restorer genotypes and methods of marker-assisted selection
JP5982288B2 (ja) 2009-12-29 2016-08-31 カッパーアールエヌエー，インコーポレイテッド 腫瘍タンパク質６３（ｐ６３）に対する天然アンチセンス転写物の阻害による腫瘍タンパク質６３関連疾患の治療
CA2785173A1 (en) 2009-12-29 2011-07-28 Curna, Inc. Treatment of nuclear respiratory factor 1 (nrf1) related diseases by inhibition of natural antisense transcript to nrf1
WO2011082304A1 (en) 2009-12-31 2011-07-07 Pioneer Hi-Bred International, Inc. Engineering plant resistance to diseases caused by pathogens
NO2521784T3 (ja) 2010-01-04 2018-05-05
CA2786741A1 (en) 2010-01-06 2011-07-14 Pioneer Hi-Bred International, Inc. Identification of diurnal rhythms in photosynthetic and non-photosynthetic tissues from zea mays and use in improving crop plants
RU2612161C2 (ru) 2010-01-06 2017-03-02 Курна, Инк. Лечение заболеваний, связанных с геном развития поджелудочной железы, путем ингибирования природного антисмыслового транскрипта к гену развития поджелудочной железы
WO2011085102A1 (en) 2010-01-11 2011-07-14 Isis Pharmaceuticals, Inc. Base modified bicyclic nucleosides and oligomeric compounds prepared therefrom
ES2664866T3 (es) 2010-01-11 2018-04-23 Curna, Inc. Tratamiento de enfermedades relacionadas con la globulina fijadora de hormonas sexuales (shbg) mediante inhibición del transcrito antisentido natural a shbg
US20110236325A1 (en) 2010-01-21 2011-09-29 NellOne Therapeutics, Inc. Methods to treat or prevent a skin condition using a nell1 peptide
CN102782135A (zh) 2010-01-25 2012-11-14 库尔纳公司 通过抑制rna酶h1的天然反义转录物而治疗rna酶h1相关疾病
US9970021B2 (en) 2010-01-26 2018-05-15 Pioneer Hi-Bred International, Inc. HPPD-inhibitor herbicide tolerance
KR101838308B1 (ko) 2010-02-22 2018-03-13 큐알엔에이, 인크. 피롤린-5-카르복실레이트 환원효소 1(ｐｙｃｒ1)에 대한 천연 안티센스 전사체의 억제에 의한 ｐｙｃｒ1과 관련된 질환의 치료
WO2011105902A2 (en) 2010-02-23 2011-09-01 Academisch Ziekenhuis Bij De Universiteit Van Amsterdam Antagonists of complement component 8-beta (c8-beta) and uses thereof
WO2011105901A2 (en) 2010-02-23 2011-09-01 Academisch Ziekenhuis Bij De Universiteit Van Amsterdam Antagonists of complement component 9 (c9) and uses thereof
JP5988436B2 (ja) 2010-02-23 2016-09-07 ジェネンテック， インコーポレイテッド 腫瘍の診断と治療のための組成物と方法
WO2011105900A2 (en) 2010-02-23 2011-09-01 Academisch Ziekenhuis Bij De Universiteit Van Amsterdam Antagonists of complement component 8-alpha (c8-alpha) and uses thereof
WO2011104128A2 (en) 2010-02-24 2011-09-01 Basf Plant Science Company Gmbh Plants having enhanced yield-related traits and a method for making the same
WO2011104155A2 (en) 2010-02-24 2011-09-01 Basf Plant Science Company Gmbh Plants having enhanced yield-related traits and a method for making the same
EP2361985A1 (en) 2010-02-26 2011-08-31 BASF Plant Science Company GmbH Plants having enhanced yield-related traits and a method for making the same
EP2361927A1 (en) 2010-02-26 2011-08-31 BASF Plant Science Company GmbH Plants having enhanced yield-related traits and a method for making the same
CA2790836A1 (en) 2010-03-03 2011-09-09 E.I. Du Pont De Nemours And Company Plant seeds with altered storage compound levels, related constructs and methods involving genes encoding oxidoreductase motif polypeptides
GB201003702D0 (en) 2010-03-05 2010-04-21 Univ Warwick Molecular engineering of a floral inducer for crop improvement
WO2011112732A2 (en) 2010-03-12 2011-09-15 The Brigham And Women's Hospital, Inc. Methods of treating vascular inflammatory disorders
EP2545173A2 (en) 2010-03-12 2013-01-16 Sarepta Therapeutics, Inc. Antisense modulation of nuclear hormone receptors
WO2011115818A1 (en) 2010-03-17 2011-09-22 Isis Pharmaceuticals, Inc. 5'-substituted bicyclic nucleosides and oligomeric compounds prepared therefrom
BR112012023505A2 (pt) 2010-03-18 2015-09-01 Basf Plant Science Co Gmbh Método para intensificar traços relacionados a rendimento em plantas em relação a plantas de controle, planta ou parte da mesma, uso de um construto, método para a produção de uma planta transgênica dotada de rendimento aumentado, planta transgênica, partes colhíveis de uma planta, produtos derivados de uma planta e uso de um ácido nucleico
EP2547195A4 (en) 2010-03-18 2014-01-08 Basf Plant Science Co Gmbh PLANTS WITH IMPROVED PERFORMANCE CHARACTERISTICS AND METHOD FOR THE PRODUCTION THEREOF
CA2793394A1 (en) 2010-03-19 2011-09-22 Basf Plant Science Company Gmbh Plants having enhanced yield-related traits and a method for making the same
CA2793388A1 (en) 2010-03-19 2011-09-22 Basf Plant Science Company Gmbh Plants having enhanced yield-related traits and a method for making the same
EP2371845A1 (en) 2010-03-22 2011-10-05 BASF Plant Science Company GmbH Plants having enhanced yield-related traits and a method for making the same
EP3517613A1 (en) 2010-04-09 2019-07-31 CuRNA, Inc. Treatment of fibroblast growth factor 21 (fgf21) related diseases by inhibition of natural antisense transcript to fgf21
EP2385129A1 (en) 2010-05-03 2011-11-09 BASF Plant Science Company GmbH Enhanced methods for gene regulation in plants
AU2011248625B2 (en) 2010-04-26 2017-01-05 Pangu Biopharma Limited Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of cysteinyl-tRNA synthetase
US8961960B2 (en) 2010-04-27 2015-02-24 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of isoleucyl tRNA synthetases
JP6005628B2 (ja) 2010-04-28 2016-10-12 アイオーニス ファーマシューティカルズ， インコーポレーテッドＩｏｎｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． 修飾ヌクレオシド、その類似体、およびこれらから調製されるオリゴマー化合物
US9127033B2 (en) 2010-04-28 2015-09-08 Isis Pharmaceuticals, Inc. 5′ modified nucleosides and oligomeric compounds prepared therefrom
WO2011139853A2 (en) 2010-04-28 2011-11-10 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of alanyl trna synthetases
US9068177B2 (en) 2010-04-29 2015-06-30 Atyr Pharma, Inc Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glutaminyl-tRNA synthetases
JP6008838B2 (ja) 2010-04-29 2016-10-19 エータイアー ファーマ， インコーポレイテッド アスパラギニルｔＲＮＡ合成酵素のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見
CA2994063A1 (en) 2010-04-29 2011-11-10 Ionis Pharmaceuticals, Inc. Modulation of transthyretin expression
CN103118693B (zh) 2010-04-29 2017-05-03 Atyr 医药公司 与缬氨酰‑tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的创新发现
US9089588B2 (en) 2010-05-03 2015-07-28 Curna, Inc. Treatment of sirtuin (SIRT) related diseases by inhibition of natural antisense transcript to a sirtuin (SIRT)
AU2011248227B2 (en) 2010-05-03 2016-12-01 Pangu Biopharma Limited Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of phenylalanyl-alpha-tRNA synthetases
EP2566515B1 (en) 2010-05-03 2017-08-02 aTyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of arginyl-trna synthetases
WO2011140135A2 (en) 2010-05-03 2011-11-10 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of methionyl-trna synthetases
KR20130079384A (ko) 2010-05-03 2013-07-10 제넨테크, 인크. 종양의 진단 및 치료를 위한 조성물 및 방법
CN102971428A (zh) 2010-05-04 2013-03-13 巴斯夫欧洲公司 对除草剂具有增加的耐受性的植物
JP6008844B2 (ja) 2010-05-04 2016-10-19 エータイアー ファーマ， インコーポレイテッド ｐ３８ＭＵＬＴＩ−ｔＲＮＡ合成酵素複合体のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見
CA2797910A1 (en) 2010-05-06 2011-11-10 Pioneer Hi-Bred International, Inc. Maize acc synthase 3 gene and protein and uses thereof
GB201007834D0 (en) 2010-05-11 2010-06-23 Vib Vzw Growth promoting fusion proteins
CN103429739B (zh) 2010-05-12 2018-11-13 哥伦比亚大学纽约管理委员会 制备产生和分泌胰岛素的肠内分泌细胞的方法
EP2569431B1 (en) 2010-05-13 2015-09-23 Sarepta Therapeutics, Inc. Methods for identifying compounds which modulate interleukins 17 and 23 signaling activity
CA2799197C (en) 2010-05-14 2019-10-29 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of phenylalanyl-beta-trna synthetases
TWI586356B (zh) 2010-05-14 2017-06-11 可娜公司 藉由抑制ｐａｒ４天然反股轉錄本治療ｐａｒ４相關疾病
CA2799480C (en) 2010-05-17 2020-12-15 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of leucyl-trna synthetases
EP2576783B1 (en) 2010-05-26 2017-11-29 CuRNA, Inc. Treatment of atonal homolog 1 (atoh1) related diseases by inhibition of natural antisense transcript to atoh1
WO2011156278A1 (en) 2010-06-07 2011-12-15 Isis Pharmaceuticals, Inc. Bicyclic nucleosides and oligomeric compounds prepared therefrom
US8846637B2 (en) 2010-06-08 2014-09-30 Isis Pharmaceuticals, Inc. Substituted 2′-amino and 2′-thio-bicyclic nucleosides and oligomeric compounds prepared therefrom
AU2011268458B2 (en) 2010-06-15 2014-06-12 Medgenics Medical Israel Ltd. Long lasting drug formulations
US20130160165A1 (en) 2010-06-24 2013-06-20 BASF Plant Science Company BmbH Plants Having Enhanced Yield-Related Traits and Method for Making the Same
AU2011268562A1 (en) 2010-06-25 2013-01-10 Basf Plant Science Company Gmbh Plants with enhanced yield-related traits and producing method thereof
WO2012003207A2 (en) 2010-07-01 2012-01-05 E. I. Du Pont De Nemours And Company Plant seeds with altered storage compound levels, related constructs and methods involving genes encoding pae and pae-like polypeptides
EA201390077A1 (ru) 2010-07-08 2013-06-28 Байер Кропсайенс Нв Белок-переносчик глюкозинолатов и его применения
CA2804416C (en) 2010-07-12 2020-04-28 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glycyl-trna synthetases
NO2593547T3 (ja) 2010-07-14 2018-04-14
EP2593555A4 (en) 2010-07-16 2014-02-26 Basf Plant Science Co Gmbh PLANTS HAVING ENHANCED YIELD LINKS AND METHOD FOR OBTAINING SAME
UA112969C2 (uk) 2010-08-03 2016-11-25 Сібас Юс Ллс Рослина, стійка до одного або більше ррх-інгібуючих гербіцидів, яка містить мутантний ген протопорфіриноген ix оксидази (ррх)
US20120122223A1 (en) 2010-08-03 2012-05-17 Cibus Us Llc Mutated protoporphyrinogen ix oxidase (ppx) genes
US9139842B2 (en) 2010-08-13 2015-09-22 Pioneer Hi-Bred International, Inc. Methods and compositions for targeting sequences of interest to the chloroplast
CA2809214A1 (en) 2010-08-24 2012-03-01 Basf Plant Science Company Gmbh Plants having enhanced yield-related traits and method for making the same
JP5964304B2 (ja) 2010-08-25 2016-08-03 エータイアー ファーマ， インコーポレイテッド チロシルｔＲＮＡ合成酵素のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見
EP2426204A1 (en) 2010-09-02 2012-03-07 Ludwig-Maximilians-Universität München Spontaneous nodule organogenesis in plants
WO2012028673A1 (en) 2010-09-02 2012-03-08 Ludwig-Maximilians-Universitaet Muenchen Spontaneous organogenesis in plants
AU2011312205B2 (en) 2010-10-05 2015-08-13 Curis, Inc. Mutant smoothened and methods of using the same
WO2012047956A2 (en) 2010-10-06 2012-04-12 Opko Curna Llc Treatment of sialidase 4 (neu4) related diseases by inhibition of natural antisense transcript to neu4
CN103517990A (zh) 2010-10-07 2014-01-15 通用医疗公司 癌症生物标志物
CN103180445B (zh) 2010-10-22 2018-02-16 库尔纳公司 通过抑制α‑L‑艾杜糖醛酸酶(IDUA)的天然反义转录物而治疗IDUA相关疾病
CN103201387B (zh) 2010-10-27 2018-02-02 库尔纳公司 通过抑制干扰素相关发育调节因子1(ifrd1)的天然反义转录物而治疗ifrd1相关疾病
WO2012063200A1 (en) 2010-11-10 2012-05-18 Basf Plant Science Company Gmbh Plants having enhanced yield-related traits and method for making the same
EP3260540A1 (en) 2010-11-12 2017-12-27 The General Hospital Corporation Polycomb-associated non-coding rnas
US8609621B2 (en) 2010-11-15 2013-12-17 E I Du Pont De Nemours And Company Acid-cleavable linkers exhibiting altered rates of acid hydrolysis
AU2011329777B2 (en) 2010-11-17 2016-06-09 Ionis Pharmaceuticals, Inc. Modulation of alpha synuclein expression
JP6071893B2 (ja) 2010-11-23 2017-02-01 カッパーアールエヌエー，インコーポレイテッド Ｎａｎｏｇへの天然アンチセンス転写物の阻害によるｎａｎｏｇ関連疾患の治療
US9834778B2 (en) 2010-12-06 2017-12-05 Basf Plant Science Company Gmbh Synthetic arcelin-5 promoter and methods of use thereof
BR112013014778A2 (pt) 2010-12-16 2017-06-06 Basf Se método para controlar a vegetação indesejável em um sítio de cultivo de plantas, método para identificar uma herbicida derivado de benzoxazinona, método de identificação de uma sequência de nucleotídeos, ácido nucleico isolado, célula vegetal transgênica, planta transgênica e semente
PL2655657T3 (pl) 2010-12-22 2019-06-28 Pioneer Hi-Bred International, Inc. Loci QTL związane z odpornością polową całej rośliny na Sclerotinię oraz sposoby jej identyfikacji
WO2012097261A2 (en) 2011-01-14 2012-07-19 The General Hospital Corporation Methods targeting mir-128 for regulating cholesterol/lipid metabolism
WO2012098517A1 (en) 2011-01-20 2012-07-26 Basf Plant Science Company Gmbh Plants having enhanced yield-related traits and method for making the same
US9688719B2 (en) 2011-01-27 2017-06-27 Ramot At Tel-Aviv University Ltd. Glycogen synthase kinase-3 inhibitors
US9243034B2 (en) 2011-01-27 2016-01-26 Ramot At Tel-Aviv University Ltd. Glycogen synthase kinase-3 inhibitors
EA030578B1 (ru) 2011-02-01 2018-08-31 Колорадо Уит Рисерч Фаундейшн, Инк. РАСТЕНИЯ, УСТОЙЧИВЫЕ К ГЕРБИЦИДАМ, ВОЗДЕЙСТВУЮЩИМ НА АЦЕТИЛ-КоА КАРБОКСИЛАЗУ
DK2670404T3 (en) 2011-02-02 2018-11-19 Univ Princeton CIRCUIT MODULATORS AS VIRUS PRODUCTION MODULATORS
KR101697396B1 (ko) 2011-02-02 2017-01-17 엑스칼리아드 파마슈티컬즈, 인코포레이티드 결합 조직 성장 인자（ctgf）를 표적으로 하는 안티센스 화합물을 사용하여 켈로이드 또는 비후성 흉터를 치료하는 방법
US9273336B2 (en) 2011-02-21 2016-03-01 E. I. Du Pont De Nemours And Company Recombinant host cells having an increase in buoyant density
AR085394A1 (es) 2011-02-25 2013-09-25 Univ Nac De La Plata Unlp Proteasa de plantas
US20130340120A1 (en) 2011-02-28 2013-12-19 Basf Plant Science Company Gmbh Plants Having Enhanced Yield-Related Traits and Producing Methods Thereof
US20140033368A1 (en) 2011-02-28 2014-01-30 Valerie Frankard Plants Having Enhanced Yield-Related Traits and Producing Methods Thereof
WO2012117368A1 (en) 2011-03-01 2012-09-07 Basf Plant Science Company Gmbh Plants having enhanced yield-related traits and producing methods thereof
US9890200B2 (en) 2011-04-12 2018-02-13 Moerae Matrix, Inc. Compositions and methods for preventing or treating diseases, conditions, or processes characterized by aberrant fibroblast proliferation and extracellular matrix deposition
CA2832910C (en) 2011-04-12 2019-07-02 Cynthia Lander Compositions and methods for preventing or treating diseases, conditions, or processes characterized by aberrant fibroblast proliferation and extracellular matrix deposition
CA2833876A1 (en) 2011-04-29 2012-11-01 Pioneer Hi-Bred International, Inc. Down-regulation of a homeodomain-leucine zipper i-class homeobox gene for improved plant performance
CA2834183A1 (en) 2011-05-19 2012-11-22 Enrique ROJO DE LA VIESCA Process for modifying the architecture and improving the yield of crop plants
CN103620036B (zh) 2011-06-09 2016-12-21 库尔纳公司 通过抑制共济蛋白(fxn)的天然反义转录物而治疗fxn 相关疾病
WO2012170347A1 (en) 2011-06-09 2012-12-13 Isis Pharmaceuticals, Inc. Bicyclic nucleosides and oligomeric compounds prepared therefrom
EP2721160A2 (en) 2011-06-14 2014-04-23 Synthon Biopharmaceuticals B.V. Compositions and methods for making and biocontaining auxotrophic transgenic plants
WO2013009935A2 (en) 2011-07-12 2013-01-17 Two Blades Foundation Late blight resistance genes
WO2013012643A1 (en) 2011-07-15 2013-01-24 Syngenta Participations Ag Polynucleotides encoding trehalose-6-phosphate phosphatase and methods of use thereof
WO2013012788A2 (en) 2011-07-15 2013-01-24 Syngenta Participations Ag Methods of increasing yield and stress tolerance in a plant
EP3112465A3 (en) 2011-08-01 2017-04-12 BASF Plant Science Company GmbH Method for identification and isolation of terminator sequences causing enhanced transcription
ES2856091T3 (es) 2011-09-14 2021-09-27 Univ Northwestern Nanoconjugados capaces de atravesar la barrera hematoencefálica
WO2013040429A1 (en) 2011-09-14 2013-03-21 Rana Therapeutics Inc. Multimeric oligonucleotide compounds
US10184151B2 (en) 2011-10-11 2019-01-22 The Brigham And Women's Hospital, Inc. Micrornas in neurodegenerative disorders
AR088515A1 (es) 2011-10-25 2014-06-18 Pioneer Hi Bred Int Metodos para alterar la composicion de la pared celular vegetal para obtener produccion de biocombustible y digestibilidad de silaje mejoradas
BR112014010537A2 (pt) 2011-10-31 2017-05-02 Pioneer Hi Bred Int método para modular a sensibilidade ao etileno, planta transgênica, proteína isolada, sequência de polinucleotídeos isolada, polipeptídeo com atividade regulatória de etileno, método para aumentar o rendimento em uma planta, método para melhorar um parâmetro agronômico de uma planta, método de seleção assistida por marcador de uma planta
JP2015502365A (ja) 2011-12-12 2015-01-22 オンコイミューニン，インコーポレイティド オリゴヌクレオチドのイン−ビボ送達
BR112014020119A2 (pt) 2012-02-13 2020-10-27 Gamida-Cell Ltd cultura de células-tronco mesenquimais
WO2013134636A1 (en) 2012-03-09 2013-09-12 Purdue Research Foundation Compositions and methods for delivery of kinase inhibiting peptides
WO2013138309A1 (en) 2012-03-13 2013-09-19 Pioneer Hi-Bred International, Inc. Genetic reduction of male fertility in plants
CN104703998B (zh) 2012-03-13 2020-08-21 先锋国际良种公司 植物中雄性育性的遗传减少
ES2694592T3 (es) 2012-03-15 2018-12-21 Curna, Inc. Tratamiento de enfermedades relacionadas con el factor neurotrófico derivado del cerebro (BDNF) por inhibición del transcrito antisentido natural de BDNF
WO2013138662A1 (en) 2012-03-16 2013-09-19 4S3 Bioscience, Inc. Antisense conjugates for decreasing expression of dmpk
WO2013154798A1 (en) 2012-04-09 2013-10-17 Isis Pharmaceuticals, Inc. Tricyclic nucleic acid analogs
WO2013154799A1 (en) 2012-04-09 2013-10-17 Isis Pharmaceuticals, Inc. Tricyclic nucleosides and oligomeric compounds prepared therefrom
JP2015518485A (ja) 2012-04-20 2015-07-02 アプタミアール セラピューティクス インコーポレイテッド 熱発生のｍｉＲＮＡ調節剤
WO2013163628A2 (en) 2012-04-27 2013-10-31 Duke University Genetic correction of mutated genes
DK2850189T3 (en) 2012-05-16 2019-02-25 Translate Bio Ma Inc COMPOSITIONS AND PROCEDURES FOR MODULATING GENEPRESSION
SG11201407483YA (en) 2012-05-16 2014-12-30 Rana Therapeutics Inc Compositions and methods for modulating smn gene family expression
US10045499B2 (en) 2012-05-24 2018-08-14 Iowa State University Research Foundation, Inc. Arabidopsis nonhost resistance gene(s) and use thereof to engineer disease resistant plants
WO2013184209A1 (en) 2012-06-04 2013-12-12 Ludwig Institute For Cancer Research Ltd. Mif for use in methods of treating subjects with a neurodegenerative disorder
AR091489A1 (es) 2012-06-19 2015-02-11 Basf Se Plantas que tienen una mayor tolerancia a herbicidas inhibidores de la protoporfirinogeno oxidasa (ppo)
EP2677035A1 (en) 2012-06-22 2013-12-25 BASF Plant Science Company GmbH Plants having enhanced yield-related traits and a method for making the same
US9567569B2 (en) 2012-07-23 2017-02-14 Gamida Cell Ltd. Methods of culturing and expanding mesenchymal stem cells
US9175266B2 (en) 2012-07-23 2015-11-03 Gamida Cell Ltd. Enhancement of natural killer (NK) cell proliferation and activity
US20150216892A1 (en) 2012-08-03 2015-08-06 Aptamir Therapeutics, Inc. Cell-specific delivery of mirna modulators for the treatment of obesity and related disorders
CN104736551B (zh) 2012-08-15 2017-07-28 Ionis制药公司 使用改进的封端方案制备寡聚化合物的方法
US10006041B2 (en) 2012-08-16 2018-06-26 Vib Vzw Means and methods for altering the lignin pathway in plants
WO2014037735A1 (en) 2012-09-10 2014-03-13 University Of Leicester Atsp1, an e3 ubiquitin ligase, and its use
US9029335B2 (en) 2012-10-16 2015-05-12 Isis Pharmaceuticals, Inc. Substituted 2′-thio-bicyclic nucleosides and oligomeric compounds prepared therefrom
CN104918639B (zh) 2012-10-22 2018-01-26 萨拜格Rfa公司 用于将治疗剂递送到活细胞和细胞核中的***
US20150299718A1 (en) 2012-11-20 2015-10-22 Rajeev Gupta Engineering Plants for Efficient Uptake and Utilization of Urea to Improve
AU2013361220A1 (en) 2012-12-21 2015-04-02 Pioneer Hi-Bred International, Inc. Compositions and methods for auxin-analog conjugation
EP2754715A1 (en) 2013-01-11 2014-07-16 Consejo Superior De Investigaciones Científicas (CSIC) Stress tolerant plants
US10231397B2 (en) 2013-01-29 2019-03-19 Basf Plant Science Company Gmbh Fungal resistant plants expressing EIN2
CA2897485A1 (en) 2013-01-29 2014-08-07 Basf Plant Science Company Gmbh Fungal resistant plants expressing hcp6
US10462994B2 (en) 2013-01-29 2019-11-05 Basf Plant Science Company Gmbh Fungal resistant plants expressing HCP7
WO2014121436A1 (en) 2013-02-05 2014-08-14 Plant Bioscience Limited Transgenic plants
US10465204B2 (en) 2013-03-08 2019-11-05 Basf Plant Science Company Gmbh Fungal resistant plants expressing MybTF
US20160002648A1 (en) 2013-03-11 2016-01-07 Mei Guo Genes for improving nutrient uptake and abiotic stress tolerance in plants
US10329574B2 (en) 2013-03-12 2019-06-25 E I Du Pont De Nemours And Company Methods for the identification of variant recognition sites for rare-cutting engineered double-strand-break-inducing agents and compositions and uses thereof
US9803214B2 (en) 2013-03-12 2017-10-31 Pioneer Hi-Bred International, Inc. Breeding pair of wheat plants comprising an MS45 promoter inverted repeat that confers male sterility and a construct that restores fertility
WO2014164074A1 (en) 2013-03-13 2014-10-09 Pioneer Hi-Bred International, Inc. Enhanced nitrate uptake and nitrate translocation by over-expressing maize functional low-affinity nitrate transporters in transgenic maize
WO2014164116A1 (en) 2013-03-13 2014-10-09 Pioneer Hi-Bred International, Inc. Functional expression of bacterial major facilitator superfamily (sfm) gene in maize to improve agronomic traits and grain yield
US20160024513A1 (en) 2013-03-14 2016-01-28 Pioneer Hi-Bred International Inc. Maize stress related transcription factor 18 and uses thereof
AU2014236181B2 (en) 2013-03-14 2020-03-19 Cibus Europe B.V. Mutated allene oxide synthase 2 (AOS2) genes
IL290273B2 (en) 2013-03-15 2024-03-01 Cibus Us Llc Methods and compositions for increasing the efficiency of targeted gene modification through the use of gene repair with oligonucleotides - mediators
IL241145B (en) 2013-03-15 2022-07-01 Cibus Us Llc Methods and compositions for increasing the efficiency of targeted gene modification using oligonucleotide-mediated gene repair
CN105247056A (zh) 2013-03-15 2016-01-13 先锋国际良种公司 Acc脱氨酶表达的调节
US9957515B2 (en) 2013-03-15 2018-05-01 Cibus Us Llc Methods and compositions for targeted gene modification
CN105143454A (zh) 2013-03-15 2015-12-09 先锋国际良种公司 Acc氧化酶多核苷酸和多肽的组合物和使用方法
US10017778B2 (en) 2013-03-21 2018-07-10 Vib Vzw Means and methods for the reduction of photorespiration in crops
AU2014259755B2 (en) 2013-05-01 2018-08-30 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating apolipoprotein (a) expression
JP6869720B2 (ja) 2013-06-13 2021-05-12 アンチセンス セラピューティクス リミテッド 併用療法
EP2816115A1 (en) 2013-06-17 2014-12-24 BASF Plant Science Company GmbH Plants having one or more enhanced yield-related traits and a method for making the same
EP3013850B1 (en) 2013-06-24 2018-07-25 Ramot at Tel-Aviv University Ltd. Glycogen synthase kinase-3 inhibitors
US11459579B2 (en) 2013-07-09 2022-10-04 Board Of Trustees Of Michigan State University Transgenic plants produced with a K-domain, and methods and expression cassettes related thereto
BR112015032956B1 (pt) 2013-07-09 2022-09-13 Board Of Trustees Of Michigan State University Método para produzir uma planta transgênica e cassete de expressão
US11162096B2 (en) 2013-10-14 2021-11-02 Ionis Pharmaceuticals, Inc Methods for modulating expression of C9ORF72 antisense transcript
CA2844640A1 (en) 2013-12-06 2015-06-06 The University Of British Columbia Method for treatment of castration-resistant prostate cancer
EP2896698A1 (en) 2014-01-17 2015-07-22 BASF Plant Science Company GmbH Plants having one or more enhanced yield-related traits and a method for making the same
WO2015116680A1 (en) 2014-01-30 2015-08-06 Two Blades Foundation Plants with enhanced resistance to phytophthora
SI3099333T1 (sl) 2014-01-31 2021-04-30 Temple University of the Commonwealth System of Higher Education 1938 Liacouras Walk BAG3 kot tarča za terapijo srčne odpovedi
ES2694857T3 (es) 2014-02-04 2018-12-27 Genentech, Inc. Smoothened mutante y métodos de uso de la misma
AU2015229095B2 (en) 2014-03-14 2022-01-27 Cibus Europe B.V. Methods and compositions for increasing efficiency of targeted gene modification using oligonucleotide-mediated gene repair
WO2015142910A1 (en) 2014-03-17 2015-09-24 Isis Pharmaceuticals, Inc. Bicyclic carbocyclic nucleosides and oligomeric compounds prepared therefrom
US10006027B2 (en) 2014-03-19 2018-06-26 Ionis Pharmaceuticals, Inc. Methods for modulating Ataxin 2 expression
WO2015143246A1 (en) 2014-03-19 2015-09-24 Isis Pharmaceuticals, Inc. Compositions for modulating ataxin 2 expression
AU2015240761B2 (en) 2014-04-01 2019-09-12 Biogen Ma Inc. Compositions for modulating SOD-1 expression
WO2015150465A2 (en) 2014-04-03 2015-10-08 Basf Se Plants having increased tolerance to herbicides
WO2015164693A1 (en) 2014-04-24 2015-10-29 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising alpha-beta-constrained nucleic acid
SG10201809953QA (en) 2014-05-01 2018-12-28 Ionis Pharmaceuticals Inc Compositions and methods for modulating complement factor b expression
WO2015171603A1 (en) 2014-05-06 2015-11-12 Two Blades Foundation Methods for producing plants with enhanced resistance to oomycete pathogens
CA2953216C (en) 2014-06-04 2020-12-22 Exicure, Inc. Multivalent delivery of immune modulators by liposomal spherical nucleic acids for prophylactic or therapeutic applications
KR102524543B1 (ko) 2014-06-10 2023-04-20 에라스무스 유니버시티 메디컬 센터 로테르담 폼페병의 치료에 유용한 안티센스 올리고뉴클레오티드
US10301624B2 (en) 2014-06-25 2019-05-28 The General Hospital Corporation Targeting human satellite II (HSATII)
US10487314B2 (en) 2014-06-26 2019-11-26 The Trustees Of Columbia University In The City Of New York Inhibition of serotonin expression in gut enteroendocrine cells results in conversion to insulin-positive cells
CA2954201A1 (en) 2014-07-08 2016-01-14 Vib Vzw Means and methods to increase plant yield
EP3169778B1 (en) 2014-07-14 2023-10-25 Washington State University Nanos knock-out that ablates germline cells
WO2016033424A1 (en) 2014-08-29 2016-03-03 Genzyme Corporation Methods for the prevention and treatment of major adverse cardiovascular events using compounds that modulate apolipoprotein b
EP3663403A1 (en) 2014-09-26 2020-06-10 University of Massachusetts Rna-modulating agents
WO2016057515A2 (en) 2014-10-06 2016-04-14 Altria Client Services Llc Genetic control of axillary bud growth in tobacco plants
AU2015350151A1 (en) 2014-11-17 2017-06-01 Moerae Matrix, Inc. Compositions and methods for preventing or treating diseases, conditions, or processes characterized by aberrant fibroblast proliferation and extracellular matrix deposition
CA2968531A1 (en) 2014-11-21 2016-05-26 Northwestern University The sequence-specific cellular uptake of spherical nucleic acid nanoparticle conjugates
US20170369902A1 (en) 2014-12-16 2017-12-28 Pioneer Hi-Bred International, Inc. Restoration of male fertility in wheat
US9688707B2 (en) 2014-12-30 2017-06-27 Ionis Pharmaceuticals, Inc. Bicyclic morpholino compounds and oligomeric compounds prepared therefrom
US10793855B2 (en) 2015-01-06 2020-10-06 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of C9ORF72 antisense transcript
WO2016115490A1 (en) 2015-01-16 2016-07-21 Ionis Pharmaceuticals, Inc. Compounds and methods for modulation of dux4
CR20170382A (es) 2015-01-21 2018-02-16 Basf Se Plantas que tienen una mayor tolerancia a herbicidas
US10793868B2 (en) 2015-02-03 2020-10-06 Institute Of Genetics And Developmental Biology Chinese Academy Of Sciences Plants with increased seed size
US10485196B2 (en) 2015-02-03 2019-11-26 The Institute Of Genetics And Developmental Biology Chinese Academy Of Scinces Rice plants with altered seed phenotype and quality
WO2016124515A1 (en) 2015-02-04 2016-08-11 Basf Plant Science Company Gmbh Method of increasing resistance against soybean rust in transgenic plants by increasing the scopoletin content
GB201501941D0 (en) 2015-02-05 2015-03-25 British American Tobacco Co Method
WO2016130600A2 (en) 2015-02-09 2016-08-18 Duke University Compositions and methods for epigenome editing
AR103649A1 (es) 2015-02-11 2017-05-24 Basf Se Hidroxifenilpiruvato dioxigenasas resistentes a herbicidas
GB201502409D0 (en) 2015-02-13 2015-04-01 British American Tobacco Co Method
US11129844B2 (en) 2015-03-03 2021-09-28 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating MECP2 expression
WO2016145234A2 (en) 2015-03-12 2016-09-15 Moerae Matrix, Inc. Use of mk2 inhibitor peptide-containing compositions for treating non-small cell lung cancer with same
US10717998B2 (en) 2015-03-18 2020-07-21 Basf Se Recombinant microorganism for improved production of fine chemicals
US10961532B2 (en) 2015-04-07 2021-03-30 The General Hospital Corporation Methods for reactivating genes on the inactive X chromosome
WO2016167780A1 (en) 2015-04-16 2016-10-20 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of c9orf72 antisense transcript
WO2016182881A1 (en) 2015-05-09 2016-11-17 Two Blades Foundation Late blight resistance gene from solanum americanum and methods of use
RU2017146342A (ru) 2015-06-04 2019-07-10 Басф Се Рекомбинантный микроорганизм для улучшенного получения химических продуктов тонкого органического синтеза
KR20180011324A (ko) 2015-06-12 2018-01-31 바스프 에스이 알라닌의 개선된 제조를 위한 재조합 미생물
US20180161429A1 (en) 2015-06-26 2018-06-14 Beth Israel Deaconess Medical Center Inc. Cancer therapy targeting tetraspanin 33 (tspan33) in myeloid derived suppressor cells
AU2016287499B2 (en) 2015-06-29 2022-08-04 Caris Science, Inc. Therapeutic oligonucleotides
CA2993652A1 (en) 2015-07-28 2017-02-02 Caris Science, Inc. Targeted oligonucleotides
EP4285912A2 (en) 2015-09-25 2023-12-06 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating ataxin 3 expression
WO2017062790A1 (en) 2015-10-09 2017-04-13 Two Blades Foundation Cold shock protein receptors and methods of use
EP4089175A1 (en) 2015-10-13 2022-11-16 Duke University Genome engineering with type i crispr systems in eukaryotic cells
EP3370734B1 (en) 2015-11-05 2023-01-04 Children's Hospital Los Angeles Antisense oligo for use in treating acute myeloid leukemia
WO2017087708A1 (en) 2015-11-19 2017-05-26 The Brigham And Women's Hospital, Inc. Lymphocyte antigen cd5-like (cd5l)-interleukin 12b (p40) heterodimers in immunity
EP3389670A4 (en) 2015-12-04 2020-01-08 Ionis Pharmaceuticals, Inc. METHODS OF TREATING BREAST CANCER
WO2017099579A1 (en) 2015-12-07 2017-06-15 Erasmus University Medical Center Rotterdam Enzymatic replacement therapy and antisense therapy for pompe disease
WO2017120365A1 (en) 2016-01-05 2017-07-13 Ionis Pharmaceuticals, Inc. Methods for reducing lrrk2 expression
CN109071625A (zh) 2016-02-04 2018-12-21 柯瑞斯公司 平滑化突变体和其使用方法
US11542515B2 (en) 2016-02-09 2023-01-03 Cibus Us Llc Methods and compositions for increasing efficiency of targeted gene modification using oligonucleotide-mediated gene repair
WO2017147087A1 (en) 2016-02-25 2017-08-31 The Brigham And Women's Hospital, Inc. Treatment methods for fibrosis targeting smoc2
JP7015243B2 (ja) 2016-03-11 2022-02-02 アルトリア クライアント サーヴィシーズ リミテッド ライアビリティ カンパニー 吸枝が減少又は消失したタバコ植物及びタバコ製品を生産する組成物及び方法
EP3429690A4 (en) 2016-03-16 2019-10-23 Ionis Pharmaceuticals, Inc. METHOD FOR MODULATING KEAP1
WO2017161168A1 (en) 2016-03-16 2017-09-21 Ionis Pharmaceuticals, Inc. Modulation of dyrk1b expression
EP3430137A4 (en) 2016-03-18 2019-11-06 Caris Science, Inc. OLIGONUCLEOTIDE THONES AND USES THEREOF
HUE056865T2 (hu) 2016-03-30 2022-03-28 Basf Se N-Butil-akrilát fermentatív elõállítása alkohol-acil-transzferáz enzim segítségével
US10563216B2 (en) 2016-04-18 2020-02-18 Bloomsburg University of Pennsylvania Compositions and methods of delivering molecules to plants
KR20230038804A (ko) 2016-04-29 2023-03-21 바스프 플랜트 사이언스 컴퍼니 게엠베하 표적 핵산의 변형을 위한 개선된 방법
EP3054014A3 (en) 2016-05-10 2016-11-23 BASF Plant Science Company GmbH Use of a fungicide on transgenic plants
EA201892517A1 (ru) 2016-05-20 2019-05-31 Басф Агро Б.В. Двойные транзитные пептиды для нацеливания полипептидов
BR112018072479B1 (pt) 2016-05-24 2023-01-31 Basf Se Método para controlar o crescimento de ervas daninhas, uso do composto de fórmula (i) e uso da composição
IL306052A (en) 2016-05-25 2023-11-01 Caris Science Inc Oligonucleotide probes and their uses
JP6995783B2 (ja) 2016-05-26 2022-02-04 ヌンヘムス、ベスローテン、フェンノートシャップ 種なし果実を実らせる植物
CA3023514A1 (en) 2016-06-17 2017-12-21 Ionis Pharmaceuticals, Inc. Modulation of gys1 expression
MX2018015798A (es) 2016-06-22 2019-07-12 Univ North Carolina State Método para incrementar la eficiencia de uso de nitrógeno y/o la eficiencia de utilización de nitrógeno en plantas.
EP3481430A4 (en) 2016-07-11 2020-04-01 Translate Bio Ma, Inc. NUCLEIC ACID CONJUGATES AND USES THEREOF
EA201990308A1 (ru) 2016-07-15 2019-07-31 Басф Се Растения с повышенной устойчивостью к гербицидам
CN109790153A (zh) 2016-07-27 2019-05-21 巴斯夫农业公司 具有增加的除草剂耐受性的植物
WO2018019845A1 (en) 2016-07-29 2018-02-01 Basf Se Method for controlling ppo resistant weeds
CA3030354A1 (en) 2016-07-29 2018-02-01 Basf Se Method for controlling ppo resistant weeds
NL2017295B1 (en) 2016-08-05 2018-02-14 Univ Erasmus Med Ct Rotterdam Antisense oligomeric compound for Pompe disease
NL2017294B1 (en) 2016-08-05 2018-02-14 Univ Erasmus Med Ct Rotterdam Natural cryptic exon removal by pairs of antisense oligonucleotides.
WO2018024696A1 (en) 2016-08-05 2018-02-08 Basf Se Method for controlling ppo resistant weeds
EP3278667A1 (en) 2016-08-05 2018-02-07 Basf Se Method for controlling ppo-inhibitor resistant weeds
WO2018024695A1 (en) 2016-08-05 2018-02-08 Basf Se Method for controlling ppo resistant weeds
US11193136B2 (en) 2016-08-09 2021-12-07 Vib Vzw Cellulose synthase inhibitors and mutant plants
EP3281523A1 (en) 2016-08-09 2018-02-14 Basf Se Method for controlling ppo resistant weeds
US20190166841A1 (en) 2016-08-09 2019-06-06 Basf Se Method for Controlling PPO Resistant Weeds
EP3281525A1 (en) 2016-08-09 2018-02-14 Basf Se Method for controlling ppo resistant weeds
AU2017311447B2 (en) 2016-08-09 2022-03-31 Basf Se Method for controlling PPO resistant weeds
US11723365B2 (en) 2016-08-09 2023-08-15 Basf Se Method for controlling PPO resistant weeds
EP3281524A1 (en) 2016-08-09 2018-02-14 Basf Se Method for controlling ppo resistant weeds
WO2018067900A1 (en) 2016-10-06 2018-04-12 Ionis Pharmaceuticals, Inc. Method of conjugating oligomeric compounds
US10647989B2 (en) 2016-10-07 2020-05-12 Altria Client Services Llc Composition and methods for producing tobacco plants and products having reduced tobacco-specific nitrosamines (TSNAs)
US11459568B2 (en) 2016-10-31 2022-10-04 University Of Massachusetts Targeting microRNA-101-3p in cancer therapy
JOP20190104A1 (ar) 2016-11-10 2019-05-07 Ionis Pharmaceuticals Inc مركبات وطرق لتقليل التعبير عن atxn3
US11033570B2 (en) 2016-12-02 2021-06-15 Cold Spring Harbor Laboratory Modulation of Lnc05 expression
WO2018112356A1 (en) 2016-12-16 2018-06-21 Two Blades Foundation Late blight resistance genes and methods of use
CN110382702A (zh) 2016-12-20 2019-10-25 巴斯夫农业公司 具有增加的除草剂耐性的植物
RU2019117393A (ru) 2016-12-27 2020-12-07 Инбиоз Н.В. Синтез сиалированных соединений in vivo
WO2018140214A1 (en) 2017-01-24 2018-08-02 Pioneer Hi-Bred International, Inc. Nematicidal protein from pseudomonas
US20190367937A1 (en) 2017-02-09 2019-12-05 Fujian Agriculture And Forestry University Expression of a phosphate transporter for improving plant yield
US11180756B2 (en) 2017-03-09 2021-11-23 Ionis Pharmaceuticals Morpholino modified oligomeric compounds
CA3060514A1 (en) 2017-04-20 2018-10-25 Atyr Pharma, Inc. Compositions and methods for treating lung inflammation
WO2018195486A1 (en) 2017-04-21 2018-10-25 The Broad Institute, Inc. Targeted delivery to beta cells
US11445692B2 (en) 2017-05-15 2022-09-20 Equi-Nom Ltd. Quantitative trait loci (QTL) associated with shatter resistant capsules in sesame and uses thereof
CN111542608A (zh) 2017-07-28 2020-08-14 双刃基金会 马铃薯y病毒抗性基因及使用方法
US11197884B2 (en) 2017-08-18 2021-12-14 Ionis Pharmaceuticals, Inc. Modulation of the notch signaling pathway for treatment of respiratory disorders
WO2019051173A1 (en) 2017-09-08 2019-03-14 Ionis Pharmaceuticals, Inc. MODULATORS OF SMAD7 EXPRESSION
US11104912B2 (en) 2017-09-11 2021-08-31 Altria Client Services Llc Compositions and methods for producing tobacco plants and products having reduced or eliminated suckers
TWI809004B (zh) 2017-11-09 2023-07-21 美商Ionis製藥公司 用於降低snca表現之化合物及方法
WO2019108619A1 (en) 2017-11-28 2019-06-06 Two Blades Foundation Methods and compositions for enhancing the disease resistance of plants
UA127971C2 (uk) 2017-11-29 2024-02-28 Басф Се Спосіб контролю за небажаною рослинністю на ділянці вирощуванння рослини
WO2019125804A1 (en) 2017-12-20 2019-06-27 Basf Se Nucleases and methods for making and using them
WO2019126641A2 (en) 2017-12-21 2019-06-27 Ionis Pharmaceuticals, Inc. Modulation of frataxin expression
US11034969B2 (en) 2017-12-22 2021-06-15 Altria Client Services Llc Plant comprising recombinant polynucleotides encoding a pigment regulatory transcription factor with a tissue-preferred promoter
CN107868123B (zh) 2017-12-25 2020-05-12 中国农业科学院作物科学研究所 一种同时提高植物产量和抗性的基因及其应用
US11359208B2 (en) 2018-01-09 2022-06-14 Cibus Us Llc Shatterproof genes and mutations
US11732271B2 (en) 2018-01-12 2023-08-22 The Sainsbury Laboratory Stem rust resistance genes and methods of use
MX2020007369A (es) 2018-01-15 2020-10-28 Ionis Pharmaceuticals Inc Moduladores de la expresion de dnm2.
AU2019210093A1 (en) 2018-01-17 2020-07-09 Basf Se Plants having increased tolerance to herbicides
BR112020014242A2 (pt) 2018-02-14 2020-12-15 Institute Of Genetics And Developmental Biology, Chinese Academy Of Sciences Métodos de aumento da eficiência de uso de nutriente
WO2019169243A1 (en) 2018-03-02 2019-09-06 Ionis Pharmaceuticals, Inc. Compounds and methods for the modulation of amyloid-beta precursor protein
MX2020009147A (es) 2018-03-02 2020-09-28 Ionis Pharmaceuticals Inc Moduladores de la expresion de irf4.
EP3768694A4 (en) 2018-03-22 2021-12-29 Ionis Pharmaceuticals, Inc. Methods for modulating fmr1 expression
WO2019186514A2 (en) 2018-03-30 2019-10-03 Rheinische Friedrich-Wilhelms-Universitat Bonn Aptamers for targeted activaton of t cell-mediated immunity
EP4062774B1 (en) 2018-04-03 2024-03-20 Altria Client Services LLC Composition and methods for producing tobacco plants and products having increased phenylalanine and reduced tobacco-specific nitrosamines (tsnas)
CN112272516B (zh) 2018-04-06 2023-05-30 儿童医疗中心有限公司 用于体细胞重新编程和调整印记的组合物和方法
MX2020010721A (es) 2018-04-11 2020-11-06 Ionis Pharmaceuticals Inc Moduladores de la expresion de ezh2.
US11732250B2 (en) 2018-04-26 2023-08-22 Basf Se Lipase enzymes
US20210115422A1 (en) 2018-05-03 2021-04-22 Basf Se Amylase enzymes
US20210355497A1 (en) 2018-05-09 2021-11-18 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing fxi expression
JP2021522800A (ja) 2018-05-09 2021-09-02 アイオーニス ファーマシューティカルズ， インコーポレーテッドＩｏｎｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． Ａｔｘｎ３発現を低減するための化合物及び方法
WO2019219933A1 (en) 2018-05-17 2019-11-21 Vib Vzw An engineered combinatorial module of transcription factors to boost production of monoterpenoid indole alkaloids
US11833168B2 (en) 2018-06-14 2023-12-05 Ionis Pharmaceuticals, Inc. Compounds and methods for increasing STMN2 expression
US11291176B2 (en) 2018-06-15 2022-04-05 Nunhems B.V. Seedless watermelon plants comprising modifications in an ABC transporter gene
MX2020013653A (es) 2018-06-27 2021-03-02 Ionis Pharmaceuticals Inc Compuestos y metodos para la reduccion de la expresion de lrrk2.
WO2020010059A1 (en) 2018-07-02 2020-01-09 Aptamir Therapeutics, Inc. Targeted delivery of therapeutic agents to human adipocytes
EP3826645A4 (en) 2018-07-25 2023-05-17 Ionis Pharmaceuticals, Inc. COMPOUNDS AND METHODS FOR REDUCING ATXN2 EXPRESSION
EP3843845A4 (en) 2018-08-29 2022-05-11 University Of Massachusetts INHIBITION OF PROTEIN KINASE FOR THE TREATMENT OF FRIEDREICH'S ATAXIA
US20230183728A1 (en) 2018-09-07 2023-06-15 Basf Plant Science Company Gmbh Improved method for the production of high levels of pufa in plants
CN113412332A (zh) 2018-09-07 2021-09-17 巴斯夫植物科学有限公司 用于在植物中产生高水平pufa的改进方法
CA3110656A1 (en) 2018-09-07 2020-03-12 Basf Plant Science Company Gmbh Improved method for the production of high levels of pufa in plants
MX2021004433A (es) 2018-10-18 2021-07-06 Basf Se Metodo para la produccion de acido acrilico o sus sales.
TW202028222A (zh) 2018-11-14 2020-08-01 美商Ionis製藥公司 Foxp3表現之調節劑
JP2022509059A (ja) 2018-11-15 2022-01-20 アイオーニス ファーマシューティカルズ， インコーポレーテッド Ｉｒｆ５発現の調節因子
CA3124395A1 (en) 2018-12-20 2020-06-25 Basf Plant Science Company Gmbh Native delivery of biomolecules into plant cells using ionic complexes with cell-penetrating peptides
MX2021008768A (es) 2019-01-22 2022-01-06 Basf Se Metodo para la produccion de acido 4-ciano benzoico o sus sales.
US20200239899A1 (en) 2019-01-24 2020-07-30 Altria Client Services Llc Tobacco Plants Comprising Reduced Nicotine and Reduced Tobacco Specific Nitrosamines
US11214803B2 (en) 2019-01-31 2022-01-04 Ionis Pharmaceuticals, Inc. Modulators of YAP1 expression
GB201902253D0 (en) 2019-02-19 2019-04-03 Univ Court Univ Of Glasgow Methods for optogenetic manipulation of stomatal function
WO2020171889A1 (en) 2019-02-19 2020-08-27 University Of Rochester Blocking lipid accumulation or inflammation in thyroid eye disease
MX2021010152A (es) 2019-02-27 2021-09-14 Ionis Pharmaceuticals Inc Moduladores de la expresion de malat1.
US20220186200A1 (en) 2019-03-11 2022-06-16 Basf Se Amylases and methods for making and using them
US20220145320A1 (en) 2019-03-14 2022-05-12 Rothamsted Research Limited Genetically modified plants with enhanced drought tolerance
EP3947665A2 (en) 2019-03-25 2022-02-09 Basf Se Amylase enzymes
EP3947664A2 (en) 2019-03-25 2022-02-09 Basf Se Amylase enzymes
WO2020193532A1 (en) 2019-03-25 2020-10-01 Basf Se Cleaning composition having amylase enzymes
CN117431244A (zh) 2019-03-29 2024-01-23 Ionis制药公司 用于调节ube3a-ats的化合物和方法
EP3966334A1 (en) 2019-05-10 2022-03-16 Basf Se Regulatory nucleic acid molecules for enhancing gene expression in plants
AU2020305509A1 (en) 2019-06-27 2022-01-20 Basf Plant Science Company Gmbh Methods for transformation of fungal spores
CN114450405A (zh) 2019-06-27 2022-05-06 双刃基金会 工程化atrlp23模式识别受体及使用方法
WO2021011348A1 (en) 2019-07-12 2021-01-21 The Regents Of The University Of California Plants with enhanced resistance to bacterial pathogens
EP3956450A4 (en) 2019-07-26 2022-11-16 Ionis Pharmaceuticals, Inc. COMPOUNDS AND METHODS FOR MODULATION OF GFAP
KR20220062517A (ko) 2019-08-15 2022-05-17 아이오니스 파마수티컬즈, 인코포레이티드 결합 변형된 올리고머 화합물 및 이의 용도
JP2022545465A (ja) 2019-08-22 2022-10-27 ビーエーエスエフ ソシエタス・ヨーロピア アミラーゼバリアント
CA3150334A1 (en) 2019-09-12 2021-03-18 Frank Meulewaeter REGULATORY NUCLEIC ACID MOLECULES TO ENHANCE GENE EXPRESSION IN PLANTS
WO2021058691A1 (en) 2019-09-26 2021-04-01 Basf Se Method for the production of beta-alanine or salts thereof
WO2021069387A1 (en) 2019-10-07 2021-04-15 Basf Se Regulatory nucleic acid molecules for enhancing gene expression in plants
AU2020396138A1 (en) 2019-12-03 2022-06-16 Basf Se Regulatory nucleic acid molecules for enhancing gene expression in plants
EP4077651A1 (en) 2019-12-16 2022-10-26 BASF Agricultural Solutions Seed US LLC Codon-optimized cas9 endonuclease encoding polynucleotide
AU2020410138A1 (en) 2019-12-16 2022-06-23 BASF Agricultural Solutions Seed US LLC Precise introduction of DNA or mutations into the genome of wheat
WO2021122080A1 (en) 2019-12-16 2021-06-24 BASF Agricultural Solutions Seed US LLC Improved genome editing using paired nickases
WO2021174019A1 (en) 2020-02-28 2021-09-02 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating smn2
EP4114954A1 (en) 2020-03-04 2023-01-11 Basf Se Method for the production of constitutive bacterial promoters conferring low to medium expression
KR20220149567A (ko) 2020-03-04 2022-11-08 바스프 에스이 이. 콜라이 및 바실루스에서의 발현을 위한 셔틀 벡터
EP4143321A2 (en) 2020-05-01 2023-03-08 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating atxn1
BR112022022933A2 (pt) 2020-05-15 2022-12-20 Basf Se Quinase 1 isolada, processos de produção de fosfato de isopentenila, construções recombinantes, vetores recombinantes, microrganismos recombinantes, composições, processos de produção de pirofosfato de isopentenila, métodos para a produção fermentativa de um ou mais isoprenoides e para produzir um microrganismo recombinante, método de cultura ou crescimento, construção de expressão e processo para bioconversão
WO2022006134A2 (en) 2020-06-29 2022-01-06 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating plp1
US11730133B2 (en) 2020-10-21 2023-08-22 Equi-Nom Ltd High yield sesame
MX2023005736A (es) 2020-11-18 2023-05-25 Ionis Pharmaceuticals Inc Compuestos y metodos para modular la expresion de angiotensinogeno.
CA3219611A1 (en) 2021-05-11 2022-11-17 Two Blades Foundation Methods for preparing a library of plant disease resistance genes for functional testing for disease resistance
CA3223192A1 (en) 2021-06-18 2022-12-22 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing ifnar1 expression
WO2023012342A1 (en) 2021-08-06 2023-02-09 Kws Vegetables B.V. Durable downy mildew resistance in spinach
WO2023031161A1 (en) 2021-09-03 2023-03-09 BASF Agricultural Solutions Seed US LLC Plants having increased tolerance to herbicides
US11395470B1 (en) 2021-09-14 2022-07-26 Equi-Nom Ltd. Sesame with high oil content and/or high yield
WO2023043220A1 (ko) 2021-09-16 2023-03-23 주식회사 큐마인 Wfdc2의 발현을 조절하는 안티센스 화합물
AU2022356378A1 (en) 2021-09-30 2024-05-02 Two Blades Foundation Plant disease resistance genes against stem rust and methods of use
WO2023067192A1 (en) 2021-10-21 2023-04-27 Consejo Superior De Investigaciones Cientificas (Csic) Methods for improving abiotic stress resistance
WO2023105244A1 (en) 2021-12-10 2023-06-15 Pig Improvement Company Uk Limited Editing tmprss2/4 for disease resistance in livestock
WO2023118136A1 (en) 2021-12-22 2023-06-29 BASF Agricultural Solutions Seed US LLC Improved screening method for genome edited events
WO2023131616A1 (en) 2022-01-05 2023-07-13 Vib Vzw Means and methods to increase abiotic stress tolerance in plants
WO2023131637A1 (en) 2022-01-06 2023-07-13 Vib Vzw Improved silage grasses
WO2023144199A1 (en) 2022-01-26 2023-08-03 Vib Vzw Plants having reduced levels of bitter taste metabolites
WO2024026474A1 (en) 2022-07-29 2024-02-01 Regeneron Pharmaceuticals, Inc. Compositions and methods for transferrin receptor (tfr)-mediated delivery to the brain and muscle
WO2024044352A1 (en) 2022-08-26 2024-02-29 The General Hospital Corporation Methods and compositions for prognosis and treatment of dilated cardiomyopathy and heart failure
WO2024083579A1 (en) 2022-10-20 2024-04-25 Basf Se Regulatory nucleic acid molecules for enhancing gene expression in plants
WO2024089011A1 (en) 2022-10-26 2024-05-02 BASF Agricultural Solutions Seed US LLC Excision of recombinant dna from the genome of plant cells
WO2024094678A2 (en) 2022-11-02 2024-05-10 Basf Se Improved method for the production of natural vanillin
WO2024098002A1 (en) 2022-11-04 2024-05-10 Regeneron Pharmaceuticals, Inc. Calcium voltage-gated channel auxiliary subunit gamma 1 (cacng1) binding proteins and cacng1-mediated delivery to skeletal muscle

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4503151A (en) * 1980-12-10 1985-03-05 Research Corporation Recombinant cDNA construction method and hybrid nucleotides useful in cloning
US4873191A (en) * 1981-06-12 1989-10-10 Ohio University Genetic transformation of zygotes
US4882279A (en) * 1985-10-25 1989-11-21 Phillips Petroleum Company Site selective genomic modification of yeast of the genus pichia
EP0260032B1 (en) * 1986-09-08 1994-01-26 Ajinomoto Co., Inc. Compounds for the cleavage at a specific position of RNA, oligomers employed for the formation of said compounds, and starting materials for the synthesis of said oligomers
US4950599A (en) * 1987-01-29 1990-08-21 Wolf Bertling Method for exchanging homologous DNA sequences in a cell using polyoma encapsulated DNA fragments
WO1990014092A1 (en) * 1989-05-18 1990-11-29 Cell Genesys, Inc. Single-strand site-directed modification of mammalian genes in vivo
JP3571337B2 (ja) * 1992-02-11 2004-09-29 セル ジェネシス，インコーポレーテッド 遺伝子標的現象による同型遺伝子接合
JPH07506252A (ja) * 1992-04-24 1995-07-13 エス・アール・アイ・インターナシヨナル 真核細胞内でのイン・ビボ相同配列ターゲッティング
EP0656747A4 (en) * 1992-08-21 1997-05-07 Univ California COMPOSITION AND METHOD FOR CHANGING DNA SEQUENCES BY HOMOLOGOUS RECOMBINATION.
AU6527094A (en) * 1993-03-31 1994-10-24 Hybridon, Inc. Modified oligonucleotides having improved anti-influenza activity

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