JPH07505639A - 自己構築ポリヌクレオチド送達システム - Google Patents
自己構築ポリヌクレオチド送達システムInfo
- Publication number
- JPH07505639A JPH07505639A JP5517793A JP51779393A JPH07505639A JP H07505639 A JPH07505639 A JP H07505639A JP 5517793 A JP5517793 A JP 5517793A JP 51779393 A JP51779393 A JP 51779393A JP H07505639 A JPH07505639 A JP H07505639A
- Authority
- JP
- Japan
- Prior art keywords
- composition
- component
- dna
- polynucleotide
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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Abstract
Description
Claims (48)
- 1.ポリヌクレオチドを真核細胞の準細胞成分にもたらすための組成物であって 、ポリヌクレオチドを上記真核細胞の細胞質膜を横断して輸送することができる 膜透過化成分に結合したポリヌクレオチドを含む上記組成物。
- 2.上記膜透過化成分が、両親媒性のカチオン性ペプチドである請求項1の組成 物。
- 3.上記ペプチドか環状ペプチドである請求項2の組成物。
- 4.上記環状ペプチドが、グラミシジンS及びチロシジンからなる群から選はれ る請求項3の組成物。
- 5.上記環状ペプチドが、グラミシジンSである請求項4組成物。
- 6.更に、リン脂質を含む請求項1の組成物。
- 7.上記リン脂質がホスファチジルエタノールアミンである請求項6の組成物。
- 8.上記ホスファチジルエタノールアミンが、ジオレオイルホスファチジルエタ ノールアミンである請求項7の組成物。
- 9.上記リン脂質がリボソーム形態である請求項6の組成物。
- 10.更に、ポリカチオンを含む請求項1の組成物。
- 11.上記ポリカチオンかポリアミンである請求項10の組成物。
- 12.上記ポリアミンが、スペルミン、スペルミジン、3,3′−ジアミノーヒ スプロピルアミン、イミノビス(N,N)−ジメチルプロピルアミン、イミノヒ ス(3−アミノプロピル)−1,3−プロパンジアミン、及びカチオン性デント リマーからなる群から選ばれる請求項11の組成物。
- 13.更に、ポリカチオンを含む請求項6の組成物。
- 14.上記膜透過化成分が、下記式を有するカチオン性胆汁酸塩である請求項1 の組成物: ▲数式、化学式、表等があります▼ 式中、X及びYは、独立して、H又はOHであり;R3は、水素、1〜10の炭 素原子を有するアルキル又はアルキルアミンであり: R4は、1〜30の炭素原子を有する正に帯電した直鎖若しくは分岐のアルキル 又はアルキルアミンであり、ここで、炭素原子の少なくとも1つはNR′で置換 されてもよく、R′は、水素、1〜10の炭素原子を有するアルキル又はアルキ ルアミンである。
- 15.ポリヌクレオチドを真核細胞の準細胞成分にもたらすための組成物であっ て、上記真核細胞を認識することができる細胞認識成分に結合したポリヌクレオ チドを含む上記組成物。
- 16.上記細胞認識成分が、上記真核細胞上の細胞表面リセプターに対するリガ ンドを含み、上記リガンドがDNA結合部分と待合している請求項15の組成物 。
- 17.上記DNA結合部分が、インターカレート剤である請求項16の組成物。
- 18.上記DNA結合部分が、主溝又は副溝バインダーである請求項16の組成 物。
- 19.上記インターカレート剤が、下記式で表される請求項17の組成物:▲数 式、化学式、表等があります▼ 式中、Zは結合てあり; n及びmは、各々独立して、1〜20の整数であり、pは0〜20の整数であり 、 Ar1及びAr2は、独立して、エチジウムプロマイド、アクリジン、ミトザン トロン、オキサゾロピリドカルバゾール、エリブチシン及びN−メチル−2,7 −ジアザピレニウム並びにそれらの誘導体からなる群から選ばれる。
- 20.上記インターカレート剤が、複数のリガンドに結合している請求項19の 組成物。
- 21.図13に示されるような、トリガラクトシル化スペルミジンビス−アクリ ジン化合物(26)。
- 22.更に、膜透過化成分を含む請求項15の組成物。
- 23.ポリヌクレオチドを真核細胞の準細胞成分にもたらすための組成物であっ て、ポリヌクレオチドを上記真核細胞の細胞質から上記真核細胞の準細胞成分に 送達することがてきる準細胞局在性成分に結合したポリヌクレオチドを含む上記 組成物。
- 24.上記準細胞成分が核であり、上記準細胞局在性成分が核局在性成分である 請求項23の組成物。
- 25.上記核局在性成分か、DNA結合部分に結合した核局在配列を含む請求項 24の組成物。
- 26.上記DNA結合部分かインターカレート剤である請求項25の組成物。
- 27.前記インターカレート剤が、下記式で表される請求項26の組成物:▲数 式、化学式、表等があります▼ 式中、Zは結合であり: n及びmは、各々独立して、1〜20の整数であり、pは0〜20の整数であり 、 Ar1、及びAr2は、独立して、エチジウムプロマイド、アクリジン、ミトザ ントロン、オキサゾロピリドカルバゾール、エリブチシン及びN−メチル−2, 7−ジアザピレニウム並びにそれらの誘導体からなる群から選ばれる。
- 28.下記式で表されるDNAマスキング成分。 ▲数式、化学式、表等があります▼ 式中、nは、6〜24の整数であり、 Yは、水素、エタノールアミン、コリン、グリセロール、セリン及びイノシトー ルからなる群から選ばれ、 R1は6〜24の炭素原子を有するアルキル又はアルケニルであり、R■は、水 素、1〜10の炭素原子を有するアルキル又はアルキルアミンであり: R4は、1〜30の炭素原子を有する正に帯電した直鎖若しくは分岐のアルキル 又はアルキルアミンであり、ここで、炭素原子の少なくとも1つはNR′で置換 されてもよく、R′は、水素、1〜10の炭素原子を有するアルキル又はアルキ ルアミンである。
- 29.真核細胞の準細胞成分ヘポリヌクレオチドをもたらすための組成物であっ て、 (a)該ポリヌクレオチド; (b)該真核細胞を認識することができる細胞認識成分;(c)該真核細胞の細 胞質膜を横断してポリヌクレオチドを輸送することができる膜透過化成分;及び 、 (d)該真核細胞の細胞質から該真核細胞の準細胞成分ヘポリヌクレオチドを送 達することができる核局在性成分; を含む上記組成物。
- 30.更に、 (e)上記ポリヌクレオチドの循環性半減期を延ばすことができるマスキング成 分: を含む請求項29の組成物。
- 31.上記マスキング成分がDNA結合部分に共有結合したポリエチレングリコ ール(PEG)である請求項30の組成物。
- 32.上記細胞認識成分、上記膜透過化成分、上記準細胞局在性成分及び上記マ スキング成分の少なくとも1つが、上記ポリヌクレオチドから分離することがで きる請求項30の組成物。
- 33.下記式で表されるインターカレート組成物:▲数式、化学式、表等があり ます▼ 式中、n及びmは、各々独立して、1〜20の整数であり、pは0〜20の整数 であり、 Ar1及びAr2は、独立して、エチジウムプロマイド、アクリジン、ミトザン トロン、オキサブゾロピリドカルバゾール、エリブチシン及びN−メチル−2, 7−ジアザピレニウム並びにそれらの誘導体からなる群から選ばれ、Xは、N− ヒドロキシサクシンイミド、マレイミド、マレイミドフェニル、ピリジルジサル ファイド、ヒドラジン及びフェニルグリオキサールからなる群から選択される反 応性基である。
- 34.上記Ar1及びAr2がアクリジンである請求項33のインターカレート 化合物。
- 35.前記式中、Xがマレイミドフェニルである請求項34のインターカレート 化合物。
- 36.下記式で表される化合物。 ▲数式、化学式、表等があります▼
- 37.下記式で表される化合物: ▲数式、化学式、表等があります▼ 式中、n及びmは、各々独立して、1〜20の整数であり、pは0〜20の整数 であり、 Ar1及びAr2は、独立して、エチジウムブロマイド、アクリジン、ミトザン トロン、オキサゾロピリドカルバゾール、エリブチシン及びN−メチル−2,7 −ジアザピレニウム並びにそれらの誘導体からなる群から選ばれ、Xは、N−ヒ ドロキシサクシンイミド、マレイミド、マレイミドフェニル、ピリジルジサルフ ァイド、ヒドラジン及びフェニルグリオキサールからなる群から選択される反応 性基であり、 Yは、細胞表面リセプターリガンド、核局在性配列及び膜透過化成分から成る群 から選択される。
- 38.上記式中、Xが下記、 ▲数式、化学式、表等があります▼ てある請求項37の化合物。
- 39.下記式で表される化合物の作製方法であって、▲数式、化学式、表等があ ります▼ 式中、n及びmは、各々独立して、1〜20の整数であり、pは0〜20の整数 てあり、 Xは、マレイミドフェニルてあり、 Ar1及びAr2は、独立して、エチジウムブロマイド、アクリジン、ミトザン トロン、オキサゾロピリドカルバゾール、エリブチシン及びN−メチル−2,7 −ジアザピレニウム並びにそれらの誘導体からなる群から選ばれ、Yは、細胞表 面リセプターりかンド、準細胞局在性配列及び膜透過化成分から成る群から選択 される; 化合物Yのフリーのスルフヒドリル基と下記式で表される成分を反応することを 含む当該作製方法。 ▲数式、化学式、表等があります▼
- 40.上記細胞を請求項29の組成物と接触すること含む、invitroで細 胞ヘポリヌクレオチドを導入する方法。
- 41.上記細胞を請求項29の組成物と接触すること含む、invivoで細胞 ヘポリヌクレオチドを導入する方法。
- 42.上記細胞を請求項29の組成物と接触すること含む、植物細胞ヘポリヌク レオチドを導入する方法。
- 43.上記細胞を請求項29の組成物と接触すること含む、哺乳細胞ヘポリヌク レオチドを導入する方法。
- 44.請求項29の組成物を含むエアロゾル組成物を哺乳類の肺へ投与すること を含む、哺乳類の肺ヘポリヌクレオチドを導入する方法。
- 45.請求項29の組成物をヒト患者へ投与することを含む、ヒト患者における 遺伝子治療方法。
- 46.上記DNA結合部分がリンカ−鎖である請求項16の組成物。
- 47.上記DNA結合部分がデンドリマーポリカチオンである請求項16の組成 物。
- 48.上記膜透過化成分がGALAのような両親媒性ペプチドである請求項1の 組成物。
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- 1993-04-05 DK DK93909508T patent/DK0636028T3/da active
- 1993-04-05 AT AT93909508T patent/ATE260679T1/de active
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Cited By (5)
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JP2008239631A (ja) * | 1996-11-12 | 2008-10-09 | Regents Of The Univ Of California | インビボ送達に有効な、脂質−核酸複合体の安定な製剤の調製 |
JP4551464B2 (ja) * | 1996-11-12 | 2010-09-29 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | インビボ送達に有効な、脂質−核酸複合体の安定な製剤の調製 |
JP2010503414A (ja) * | 2006-09-15 | 2010-02-04 | エンゾン ファーマスーティカルズ インコーポレイテッド | 正に荷電した部分を含有するポリマー複合体 |
JP2013519662A (ja) * | 2010-02-12 | 2013-05-30 | プロカルタ バイオシステムズ リミテッド | 核酸複合体 |
JP2013523111A (ja) * | 2010-04-01 | 2013-06-17 | プロカルタ バイオシステムズ リミテッド | 転写因子デコイ |
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DK0636028T3 (da) | 2004-07-12 |
JP4074658B2 (ja) | 2008-04-09 |
DE69333434T2 (de) | 2005-03-03 |
AU682308B2 (en) | 1997-10-02 |
EP0636028A4 (en) | 1998-12-09 |
EP0636028B1 (en) | 2004-03-03 |
PT636028E (pt) | 2004-07-30 |
JP2004000245A (ja) | 2004-01-08 |
EP1236473A3 (en) | 2003-01-15 |
JP2007006899A (ja) | 2007-01-18 |
JP3950472B2 (ja) | 2007-08-01 |
JP2005110696A (ja) | 2005-04-28 |
AU682308C (en) | 2006-08-17 |
JP3688278B2 (ja) | 2005-08-24 |
US5977084A (en) | 1999-11-02 |
ATE260679T1 (de) | 2004-03-15 |
WO1993019768A1 (en) | 1993-10-14 |
US6300317B1 (en) | 2001-10-09 |
ES2221920T3 (es) | 2005-01-16 |
DE69333434D1 (de) | 2004-04-08 |
CA2133323A1 (en) | 1993-10-14 |
AU4027893A (en) | 1993-11-08 |
EP0636028A1 (en) | 1995-02-01 |
US5955365A (en) | 1999-09-21 |
EP1236473A2 (en) | 2002-09-04 |
CA2133323C (en) | 2010-10-26 |
JP3907662B2 (ja) | 2007-04-18 |
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