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KR950703649A - 결함 아데노비루스 벡터 및 유전자 치료에서 그의 사용 - Google Patents

결함 아데노비루스 벡터 및 유전자 치료에서 그의 사용 Download PDF

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KR950703649A
KR950703649A KR1019950700975A KR19950700975A KR950703649A KR 950703649 A KR950703649 A KR 950703649A KR 1019950700975 A KR1019950700975 A KR 1019950700975A KR 19950700975 A KR19950700975 A KR 19950700975A KR 950703649 A KR950703649 A KR 950703649A
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페리꼬데 미셀
비네 엠마누엘
예 빠트리스
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필리쁘 베케르
로오느-푸우랜크 로레르 소시에테 아노님
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Abstract

신규한 아테노비루스 유래 비루스벡터, 그의 제법 및 유전자 치료에서 그의 사용이 기재된다.

Description

결함 아대노비루스 벡터 및 유전자 치료에서 그의 사용
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도 Ad5아데노비루스의 유전자 구조. Ad5의 완전한 서열은 데이타베이스상 입수가능하고 당업자가 임의의 제한 부위를 선택하거나, 생성하여, 임의의 게놈 영역을 단리할 수 있게한다.
제2도 CAV2 아데노비루스 Manhattan 균주의 제한 지도(앞서 인용한 Spibey일동에 따름).
제3도 결찰에 의한 본 발명의 결함 비루스 구성.

Claims (30)

  1. -ITR 서열-캡슐화를 허용하는 서열-이종 DNA서열로 구성되고 E1 유전자 및 적어도 하나의 E2, E4 및 L1-L5 유전자가 비-기능성인 결함 재조함 아세노비루스.
  2. 제1항에 있어서, 인간, 동물 또는 혼합된 공급원의 것임을 특징으로 하는 아데노비루스.
  3. 제2항에 있어서, 인간 기원의 아데노비루스가 C군으로 분류된 것들로부터, 바람직하게 유형 2 또는 5 아데노비루스(Ad2 또는 Ad5)로부터 선택되는 것을 특징으로 하는 아데노비루스.
  4. 제2항에 있어서, 동물 기원의 아데노비루스가 개, 소, 쥐, 양, 돼지, 새 또는 원숭이 기원의 아데노비루스로부터 선택되는 것을 특징으로 하는 아데노비루스.
  5. 제1-4항 중 임의의 한 항에 있어서, 적어도 E1 및 E4유전자가 비-기능성인 것을 특징으로 하는 아데노비루스.
  6. 제1-5항중 임의의 한 항에 있어서, 후반 유전자가 없는 것을 특징으로 하는 아데노비루스.
  7. 제1항에 있어서, 하기로 구성되는 것을 특징으로 하는 아데노비루스: -ITR서열- 캡슐화를 허용하는 서열- 이종 DNA 서열, 및- 유전자 또는 유전자 E2의 부분을 운반하는 영역.
  8. 제1항에 있어서, 하기로 구성되는 것을 특징으로 하는 아데노비루스: -ITR 서열- 캐슐화를 허용하는 서열- 이종 DNA 서열, 및-유전자 또는 유전자 E4의 부분을 운반하는 영역.
  9. 제1항에 있어서, E1, E3 및 E4유전자가 그의 게놈으로부터 삭제되는 것을 특징으로 하는 아데노비루스.
  10. 제1항에 있어서, E1, E3, L5 및 E4유전자가 그의 게놈으로부터 삭제되는 것을 특징으로 하는 아데노비루스.
  11. 제1-10항 중 임의의 한 항에 있어서, 이종 촉진제의 제어하에 기능성 유전자 E3을 부가로 포함하는 것을 특징으로 하는 아데노비루스.
  12. 제1-11항 중 임의의 한 항에 있어서, 이종 DNA 서열이 하나 이상의 치료 유전자 및/또는 항원 펩티드를 암호화하는 하나 이상의 유전자를 함유하는 것을 특징으로 하는 아데노비루스.
  13. 제12항에 있어서, 치료 유전자가 효소, 혈액 유도체, 호르몬, 림포킨(인터로이킨, 인터페론, TNF등), 성장 인자, 신경전달제 또는 상기의 선구체 또는 합성 효소, 영양 인자(BDNF, CNTF, NGF, IGF. GMF, aFGF, bFGF, NT3, NT5 등) 아폴리포프로테인(ApoAI, ApoAIV, ApoE 등) 디스트로핀 또는 미니디스트로핀, 종양 억제 유전자를 코딩하는 유전자 또는 혈액응고와 관련된 인자(인자 Ⅶ, Ⅷ, Ⅸ등)를 코딩하는 유전자로부터 선택되는 것을 특징으로 하는 아데노비루스.
  14. 제12항에 있어서, 치료 유전자가 그의 타켓 세포내 발현이 유전자의 발현 또는 세포상 mRNA의 전사를 제어가능하게 하는 안티센스 유전자 또는 서열인 것을 특징으로 하는 아데노비루스.
  15. 제12항에 있어서, 유전자가 미생물 또는 비루스에 대한 인간내 면역 반응을 발생시킬 수 있는 항원 펩티드를 코딩하는 것을 특징으로 하는 아데노비루스.
  16. 제15항에 있어서, 유전자가 Epstein Barr 비루스, HIV 비루스, B형 간염 비루스, 가성-관경병 비루스에 대한 특이성인 항원 펩티드 또는 대안으로 종양에 대해 특이성인 펩티드를 코딩하는 것을 특징으로 하는 아데노비루스.
  17. 제1-16항 중 임의의 한 항에 있어서, 이종 DNA 서열이 또한 치료 유전자의 및/또한 감염 세포내 항원 펩티드를 코딩하는 유전자의 발현을 허용하는 서열로 구성되는 것을 특징으로 하는 아데노비루스.
  18. 제1-17항 중 임의의 한 항에 있어서, 이종 DNA 서열이 치료 유전자의 업스트림. 타갯 세포의 비밀 경로로 합성되는 치료학적 생성물을 지시하는 시그날 서열로 구성되는 것을 특징으로 하는 아데노비루스.
  19. 제1-18항 중 임의의 한 항에 따른 결함 재조합 아데노비루스의 보충에 필요한, 그의 개놈 내로 통합된, 기능성으로 구성된 아데노비루스에 의해 간염될 수 있는 세포라인.
  20. 제19항에 있어서, 그의 개놈내, 아데노비루스로부터의 적어도 E1 및 E2 유전자를 함유한 것을 특징으로 하는 세포라인.
  21. 제20항에 있어서, 아데노비루스로부터의 E4유전자를 부가로 함유한 것음 특징으로 하는 세포라인.
  22. 제19항에 있어서, 그의 게놈내, 아데노비루스로부터의 적어도 E1 및 E4유전자를 함유한 것을 특징으로 하는 세포라인.
  23. 제19-22항중 임의의 한 항에 있어서, 글루코코르티코이드 수용체를 위한 유전자를 부가로 함유한 것을 특징으로 하는 세포라인.
  24. 제19-23항중 임의의 한 항에 있어서, E2 및 E4 유전자가 유도가능한 촉진제의 제어하에 있는 것을 특징으로 하는 세포라인.
  25. 제24항에 있어서, 유도가능한 촉진제가 MMTV의 LTR촉진제인 것을 특징으로 하는 세포라인.
  26. 제19-25항중 임의의 한 항에 있어서, E2 유전자가 72K 단백질을 코딩하는 것을 특징으로 하는 세포라인.
  27. 제19-26항중 임의의 한 항에 있어서, 라인 293으로부터 얻어지는 것을 특징으로 하는 세포라인.
  28. 제1-18항중 임의의 한 항에 따른 적어도 하나의 결합 재조합 아데노비루스로 구성되는 제약학적 조성물.
  29. 제28항에 있어서, 제 5-10항중 임의의 한 항에 따른 재조합 아데노비루스로 구성되는 제약학적 조성물.
  30. 제28항 또는 29항에 있어서, 주사가능 배합물을 위해 제약학적으로 허용 가능한 부형재로 포함하는 제약학적 조성물.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019950700975A 1993-07-13 1994-07-08 결함아데노바이러스벡터및유전자치료에서그의사용 Expired - Fee Related KR100356615B1 (ko)

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