KR970706829A - 유전자 발현을 하향 조절하기 위한 2'-치환된 올리고누클레오티드의 사용방법(use of 2' -substituted oligonucleotides to down-regulating gene expression) - Google Patents

유전자 발현을 하향 조절하기 위한 2'-치환된 올리고누클레오티드의 사용방법(use of 2' -substituted oligonucleotides to down-regulating gene expression)

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KR970706829A
KR970706829A KR1019970702715A KR19970702715A KR970706829A KR 970706829 A KR970706829 A KR 970706829A KR 1019970702715 A KR1019970702715 A KR 1019970702715A KR 19970702715 A KR19970702715 A KR 19970702715A KR 970706829 A KR970706829 A KR 970706829A
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oligonucleotide
gene
complementary
group
nucleotides
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아그라월 서드허
비. 디아지오 로버트
장 루이웬
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다알렌 에이. 반스톤
하이브리돈, 인코포레이티드
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Abstract

본 발명은 유전자에 상보성인 올리고누클레오티드를 포함하는 약리학적 제형을 동물에 경구 투여하여, 동물체내에서 유전자의 발현을 하향 조절하는 방법에 관한 것이다. 투여되는 올리고누클레오티드는 비-포스포디에스테르 누클레오티드간 결합을 갖고, 하나 이상의 2'-치환된 리보누클레오티드를 포함하며, 상기 올리고누클레오티드는 유전자의 생성물의 발현을 억제하여, 유전자의 발현을 하향 조절한다.

Description

유전자 발현을 하향 조절하기 위한 2'-치환된 올리고누클레오티드의 사용방법(USE OF 2' -SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION )
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (15)

  1. 약제학적으로 허용되는 담체 중에서 유전자에 상보성이고, 비-포스포디에스테르 누클레오티드간 결합을 갖고 하나 이상의 2'-치환된 리보누클레오티드를 포함하며 유전자의 생성물의 발현을 억제하는 올리고누클레오티드를 포함하는 약제학적 제형을 경구 투여하여 유전자의 발현을 하향 조절하는 단계를 포함하는, 동물체내에서 유전자의 발현을 하향 조절하는 방법.
  2. 제1항에 있어서, 올리고누클레오티드가 3' 및 5' 말단을 갖고, 2'-치환된 리보누클레오티드가 3' 말단에 있음을 특징으로 하는 방법.
  3. 제2항에 있어서, 올리고누클레오티드가 5' 말단에서 하나 이상의 2'-치환된 리보누클레오티드를 추가로 함유함을 특징으로 하는 방법.
  4. 제1항에 있어서, 올리고누클레오티드 중의 누클레오티드가 모두 2'-치환된 리보누클레오티드임을 특징으로 하는 방법.
  5. 제1항에 있어서, 2'-치환된 리보누클레오티드가 2'-0-알킬 리보누클레오티드임을 특징으로 하는 방법.
  6. 제1항에 있어서, 올리고누클레오티드가 하나 이상의 데옥시리보누클레오티드를 포함함을 특징으로 하는 방법.
  7. 제6항에 있어서, 올리고누클레오티드가 RNase H를 활성화시킬 수 있는 4개 이상의 인접 데옥시리보누클레오티드의 영역을 포함함을 특징으로 하는 방법.
  8. 제1항에 있어서, 올리고누클레오티드가 알킬포스포네이트, 포스포로티오에이트, 포스포로디티오에이트, 알킬포스포노티오에이트, 포스포라미데이트, 포스포라미다이트, 포스페이트 에스테르, 카르바메이트, 카아보네이트, 포스페이트 트리에스테르, 아세트아미데이트 및 카르복시메틸 에스테르로 구성된 군으로부터 선택된 누클레오티드간 결합을 포함함을 특징으로 하는 방법.
  9. 제8항에 있어서, 누클레오티드가 모두 포스포로티오에이트 또는 포스포로디티오에이트 누클레오티드간 결합을 통해 결합됨을 특징으로 하는 방법.
  10. 제1항에 있어서, 올리고누클레오티드가 변형됨을 특징으로 하는 방법.
  11. 제1항에 있어서, 올리고누클레오티드가 바이러스의 유전자, 병원균 유기체 또는 세포 유전자에 상보성임을 특징으로 하는 방법.
  12. 제11항에 있어서, 올리고누클레오티드가 AIDS, 구강 또는 생식기 포진, 유두종, 인풀루엔자, 발 및 구강질환 황열, 수두, 대상 포진, 성숙T-세포 백혈병, 버키트 림프종, 비인두암 및 간염으로 구성된 군으로부터 선택된 질환에 수반되는 바이러스의 유전자에 상보성임을 특징으로 하는 방법.
  13. 제1항에 있어서, 올리고누클레오티드가 알쯔하이머병과 관련된 단백질을 코드화시키는 유전자에 상보성임을 특징으로 하는 방법.
  14. 제1항에 있어서, 올리고누클레오티드가 아메바증, 차가스병, 주혈원충병, 뉴시토시스, 편모충증, 크립토포리디오시스, 트리코모니아시스, 말라리아, 회충증, 필라리아병, 선모충증 또는 주혈흡충병 감염으로 구성된 군으로부터 선택된 기생충 질환을 유발시키는 기생충에서 단백질을 코드화시키는 유전자에 상보성임을 특징으로 하는 방법.
  15. 제1항에 있어서, 올리고누클레오티드가 HIV 유전자에 상보성이고, 포스포로티오에이트 누클레오티드간 결합에 의해 결합된 15 내지 26개의 누클레오티드를 포함하며, 3'말단에서 상기 누클레오티드 중 하나 이상은 2'-치환된 리보누클레오티드이고, 4개 이상의 누클레오티드는 인접 데옥시리보누클레오티드임을 특징으로 하는 방법.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019970702715A 1994-10-25 1995-10-17 유전자 발현을 하향 조절하기 위한 2'-치환된 올리고누클레오티드의 사용방법(use of 2' -substituted oligonucleotides to down-regulating gene expression) KR970706829A (ko)

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US08/328,520 1994-10-25
US08/328,520 US5591721A (en) 1994-10-25 1994-10-25 Method of down-regulating gene expression
PCT/US1995/013069 WO1996012497A1 (en) 1994-10-25 1995-10-17 Use of 2'-substituted oligonucleotides to down-regulating gene expression

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US (1) US5591721A (ko)
EP (1) EP0788366B1 (ko)
JP (1) JP3926840B2 (ko)
KR (1) KR970706829A (ko)
CN (1) CN1170367A (ko)
AT (1) ATE187645T1 (ko)
AU (1) AU3893095A (ko)
CA (1) CA2203652C (ko)
DE (1) DE69513998T2 (ko)
DK (1) DK0788366T3 (ko)
ES (1) ES2141393T3 (ko)
GR (1) GR3032669T3 (ko)
NO (1) NO971905L (ko)
PT (1) PT788366E (ko)
WO (1) WO1996012497A1 (ko)

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