KR100880701B1 - 증식성 질환 치료용 아데노바이러스 벡터 및 p53 유전자의재조합 유전자 약제 - Google Patents
증식성 질환 치료용 아데노바이러스 벡터 및 p53 유전자의재조합 유전자 약제 Download PDFInfo
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Abstract
Description
아데노바이러스 5의 우측 말단-
본 발명의 재조합 P53 아데노바이러스는 실험시 많은 악성 종양의 치료용 약제로서 제조할 수 있다. 그리고 종양신생 및 수술-후 종양 재발 방지용 약제로도 제조할 수 있다.
본 출원인들은 또한 재조합 P53 아데노바이러스가 비정상적 과증식 세포 발현 정상 p53 단백질을 유도할 수 있으며, 따라서 효과적으로 세포 재생을 억제하고 켈로이드를 포함하는 과증식성 질환을 회복시킨다는 것을 발견하였다.
발명의 요약
본 발명의 목적은 그들의 벡터를 가진면서 잠재적으로 치료 유전자를 재조합하는 것이며, 따라서 과증식증을 치료하기 위한 아데노바이러스 벡터의 재조합 DNA와 p53 유전자를 제공하는 것이다. 재조합 생성물을 이후 과증식성 세포 발현 정상 P53 단백질을 유도하게 된다. 이런 방식으로 비정상 세포의 증식을 효과적으로 억제하고 켈로이드를 비롯한 과증식성 질환을 치유하는데 사용할 수 있다.
본 발명에 사용된 293 세포(ATCC CRL-1573, 32번째 세대, 1997년 6월 13일, ATCC로부터 입수)를 아데노바이러스 5(Ad5) DNA에 의해 형질전환되고 Ad5 5' 말단으로부터의 11 %의 유전자(E1a 포함)를 함유하는 인간 배아 신장 내피 세포로부터 스크리닝하였다. 상기 세포는 아데노바이러스에 의한 감염에 대해 상당히 허용적이었으며, 아데노바이러스의 성장에 대해서도 허용적이었다.
Claims (9)
- 아데노바이러스 벡터 및 p53 유전자 발현 카세트를 포함하는 재조합 아데노바이러스 벡터를 포함하는, 임의의 종류의 반흔(scar) 치료용 약학 조성물.
- 제1항에 있어서, 재조합체의 아데노바이러스 벡터 및 p53 유전자 발현 카세트가 프로모터-p53cDNA-폴리 아데노신으로 구성된 특이적 서열인 약학 조성물.
- 제2항에 있어서, 상기 유전자 발현 카세트의 상류(upstream)가 임의의 진핵 세포 프로모터, 원핵 세포 프로모터 또는 바이러스 프로모터이고, 하류(downstream)가 임의의 진핵 유전자 폴리 아데노신 잔기(폴리 A 테일)인 약학 조성물.
- 제1항에 있어서, 상기 재조합체는1) 원핵 세포에서 아데노바이러스 및 플라스미드 pGT-1(아데노바이러스의 양 말단 상에 두 개의 역 말단 반복을 함유)의 상동성 재조합에 의해 재조합 pGT-2를 얻고,2) 원핵 세포에서 상기 pGT-2 및 인공 서열 "아데노바이러스의 우측 아암/프로모터-p53cDNA-폴리 A/아데노바이러스의 좌측 아암"의 상동성 재조합에 의해 재조합 pGT-3을 얻고, 및3) 엔도뉴클레아제(endonuclease) PacI을 사용하여 원핵 서열을 제거함으로써 재조합 p53 아데노바이러스를 얻는 것을 포함하는, 상동성 재조합에 의해 원핵 세포에서 얻는 것인 약학 조성물.
- 제4항에 있어서, 원핵 세포가 대장균(E. coli)인 약학 조성물.
- 삭제
- 제1항에 있어서, 반흔이 병리학적 반흔인 약학 조성물.
- 제7항에 있어서, 병리학적 반흔이 켈로이드인 약학 조성물.
- 제1항에 있어서, 주사액인 약학 조성물.
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Application Number | Priority Date | Filing Date | Title |
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CN03125129.3 | 2003-05-10 | ||
CNB031251293A CN1327899C (zh) | 2003-05-10 | 2003-05-10 | 腺病毒载体与p53基因的基因重组体的应用 |
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KR20060029216A KR20060029216A (ko) | 2006-04-05 |
KR100880701B1 true KR100880701B1 (ko) | 2009-02-02 |
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US (1) | US20090215164A1 (ko) |
EP (1) | EP1642981B1 (ko) |
JP (1) | JP4695086B2 (ko) |
KR (1) | KR100880701B1 (ko) |
CN (1) | CN1327899C (ko) |
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RU2392319C2 (ru) * | 2003-03-06 | 2010-06-20 | Жаохи ПЕНГ | Рекомбинантный вирус, построенный с использованием вектора вируса и гена-подавителя опухоли человека, а также его применение |
BR122013008865B8 (pt) * | 2004-05-26 | 2021-05-25 | Psioxus Therapeutics Ltd | adenovírus oncolítico de replicação competente |
CN1966683B (zh) * | 2005-11-17 | 2010-05-12 | 王尚武 | 表达新型肿瘤抑制基因p53的重组腺病毒 |
CN102586327B (zh) * | 2012-01-18 | 2013-09-11 | 陕西师范大学 | 一步法构建携带外源基因的d24纤维蛋白修饰的条件复制型腺病毒载体及其应用 |
CN104357408A (zh) * | 2014-03-13 | 2015-02-18 | 哈尔滨博翱生物医药技术开发有限公司 | 一种重组新城疫病毒及其应用 |
CN110055227A (zh) * | 2019-03-13 | 2019-07-26 | 中国人民解放军第四军医大学 | 用于增生性瘢痕治疗的野生型p53腺病毒及纯化的制备方法 |
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WO1998040508A1 (en) * | 1997-03-14 | 1998-09-17 | Selective Genetics, Inc. | Adenoviral vectors with modified tropism |
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WO1995016772A1 (en) * | 1993-12-14 | 1995-06-22 | Cornell Research Foundation, Inc. | Adenovirus gene expression system |
AU4502096A (en) * | 1994-11-11 | 1996-06-06 | Arch Development Corporation | A process of inhibiting non-neoplastic pathological cell proliferation |
US6495526B2 (en) * | 1996-01-23 | 2002-12-17 | Gpc Biotech, Inc. | Inhibitors of cell-cycle progression and uses related thereto |
AU759164C (en) * | 1997-11-19 | 2007-03-29 | Georgetown University | Targeted liposome gene delivery |
WO1999050287A2 (en) * | 1998-03-27 | 1999-10-07 | The Johns Hopkins University | P40 protein acts as an oncogene |
AU2001265219A1 (en) * | 2000-05-31 | 2001-12-11 | Human Gene Therapy Research Institute | Methods and compositions for efficient gene transfer using transcomplementary vectors |
CN1177057C (zh) * | 2002-05-08 | 2004-11-24 | 彭朝晖 | 病毒载体与人肿瘤抑制基因的重组体及其应用 |
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JP4695086B2 (ja) | 2011-06-08 |
EP1642981B1 (en) | 2011-06-15 |
AU2004240968A1 (en) | 2004-12-02 |
JP2007504274A (ja) | 2007-03-01 |
ATE513050T1 (de) | 2011-07-15 |
KR20060029216A (ko) | 2006-04-05 |
CA2525304A1 (en) | 2004-12-02 |
CN1327899C (zh) | 2007-07-25 |
EP1642981A1 (en) | 2006-04-05 |
WO2004104204A1 (fr) | 2004-12-02 |
EP1642981A4 (en) | 2006-09-06 |
CN1471977A (zh) | 2004-02-04 |
AU2004240968B2 (en) | 2008-04-17 |
US20090215164A1 (en) | 2009-08-27 |
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