KR20080083031A - 내피세포 특이성을 나타내는 프로모터 및 이를 이용하는방법 - Google Patents
내피세포 특이성을 나타내는 프로모터 및 이를 이용하는방법 Download PDFInfo
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Abstract
Description
플라스미드 | 루시페라아제 활성: 내피세포주 | 비내피세포주 | |
HUVAC | BAEC | RIN | |
PPE-1 | 135.12 | 1121.3 | 0.73 |
PPE-1-3X | 768 | 18331.7 | 0.32 |
주입 후 일수 | 5 | 14 | ||
광 유닛/㎍ 단백질 | 광 유닛/㎍ 단백질 | |||
조직 | PPE-1 | CMV | PPE-1 | CMV |
대동맥 | 13.0±2.9 (32.7%) | 1.4±0.5 (0.56%) | 0.6±2.4 (12.6%) | 1.3±0.3 (1.1%) |
심장 | 0.2±0.1 (0.55) | 1±0.6 (0.4%) | 1.5±0.3 (1.7%) | 1.8±0.6 (1.6%) |
간 | 22.7±4.5 (57%) | 219±111.5 (88.6%) | 34.9±7.8 (41.6%) | 52.8±10.6 (46.8%) |
폐 | 0.2±0.1 (0.5%) | 2.3±1.0 (0.9%) | 3.6±0.8 (4.3%) | 2.0±0.9 (1.8%) |
근육 | 0.3±0.1 (0.7%) | 0.8±0.2 (0.3%) | 1.2±0.3 (1.4%) | 1.5±0.5 (1.3%) |
비장 | 1.3±0.8 (3.2%) | 1.6±0.9 (0.6%) | 2.0±0.4 (2.4%) | 2.3±0.9 (2.0%) |
체장 | 2±0.6 (5.0%) | 20.1±6.8 (8.1%) | 26.4±5.9 (31.5%) | 45.2±24.5 (40.1%) |
신장 | 0.1±0 (0.25%) | 0.9±0.6 (0.4%) | 0.6±0.1 (0.71%)) | 0.8±0.3 (0.7%) |
MOI=1 | MOI=5 | MOI=10 | |
Ad5PPE-1 | 8.1±0.06 | 33.95±7.0 | 50.7±5.0 |
Ad5CMV | 9.3±1.1 | 47.3±4.0 | 88.13±10.1 |
Claims (19)
- 내피세포 내에서 프로모터로서 기능하는 분리된 폴리뉴클레오티드로서, 서열번호: 8에 기재되어 있는 서열의 하나 이상의 카피를 갖는 인핸서 요소 및 내피세포 특이적 프로모터 요소로 이루어진 분리된 폴리뉴클레오티드.
- 제 1 항에 있어서, 상기 인핸서 요소가 서열번호: 6에 기재된 서열의 하나 이상의 카피를 추가로 갖는 것인 분리된 폴리뉴클레오티드.
- 제 1 항에 있어서, 상기 인핸서 요소가 서열번호: 8에 기재된 서열의 카피 하나 및 서열번호: 6에 기재된 서열의 둘 이상의 카피로 이루어진 것인 분리된 폴리뉴클레오티드.
- 제 1 항에 있어서, 상기 내피세포 특이적 프로모터 요소가 PPE-1 프로모터의 하나 이상의 카피로 이루어진 것인 분리된 폴리뉴클레오티드.
- 제 1 항에 있어서, 서열번호: 5에 기재된 서열의 하나 이상의 카피로 이루어진 저산소증 반응 요소를 추가로 갖는 분리된 폴리뉴클레오티드.
- 제 1 항에 있어서, 상기 인핸서 요소가 서열번호: 7에 기재된 것인 분리된 폴리뉴클레오티드.
- 제 1 항의 분리된 폴리뉴클레오티드, 및 VEGF, PDGF-BB, EGR-1, FGF 및 p55로 이루어진 군에서 선택된 관심대상 핵산 서열을 갖는 핵산 구조체로서, 상기 관심대상 핵산 서열이 상기 분리된 폴리뉴클레오티드의 조절 제어를 받는 것인 핵산 구조체.
- 제 1 항의 분리된 폴리뉴클레오티드로 형질 변환된 포유류 세포.
- 혈관신생 조절을 필요로 하는 대상에서의 혈관신생 조절을 위한 의약으로서, 내피세포 특이적 프로모터의 조절 제어를 받도록 위치한 관심대상 핵산 서열의 내피세포 내에서의 발현에 사용되는 핵산 구조체, 및 서열번호: 8에 기재된 서열의 하나 이상의 카피를 갖는 내피세포 조절요소를 포함하는 의약.
- 제 9 항에 있어서, 상기 프로모터가 서열번호: 1에 기재된 PPE-1 프로모터인 의약.
- 제 9 항에 있어서, 상기 인핸서 요소가 서열번호: 6에 기재된 서열의 하나 이상의 카피를 추가로 갖는 것인 의약.
- 제 11 항에 있어서, 상기 인핸서 요소가 서열번호:7에 기재된 것인 의약.
- 제 11 항에 있어서, 상기 서열번호: 6에 기재된 서열의 하나 이상의 카피가 두 개의 카피를 갖는 것인 의약.
- 제 13 항에 있어서, 상기 서열번호: 6에 기재된 서열의 하나 이상의 카피가 인접해 있는 것인 의약.
- 제 11 항에 있어서, 상기 관심대상 핵산 서열이 VEGF, PDGF-BB, EGR-1, FGF 및 p55로 이루어진 군에서 선택되는 것인 의약.
- 제 11 항에 있어서, 하기로 이루어진 군에서 선택된 방법에 의해 투여되도록 제형화된 것인 의약:(i) 전신성 생체내 투여;(ii) 대상의 신체로부터 제거된 세포로의 생체외 투여, 및 이어서 상기 세포를 상기 대상의 상기 신체 내로 재도입; 및(iii) 국소적 생체내 투여.
- 제 9 항에 있어서, 상기 조절은 혈관신생을 저해하는 것이고, 상기 관심대상 핵산서열은 p55인 의약.
- 제 9 항에 있어서, 상기 조절은 혈관신생을 증대시키는 것이고, 상기 관심대상 핵산서열은 VEGF, PDGF-BB, EGR-1 및 FGF로 이루어진 군에서 선택되는 것인 의약.
- 제 9 항에 있어서, 서열번호: 5에 기재된 서열의 하나 이상의 카피를 추가로 포함하는 의약.
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US24858200P | 2000-11-17 | 2000-11-17 | |
US60/248,582 | 2000-11-17 |
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KR1020037006728A Division KR100869814B1 (ko) | 2000-11-17 | 2001-11-15 | 내피세포 특이성을 나타내는 프로모터 및 이를 이용하는 방법 |
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KR1020037006728A KR100869814B1 (ko) | 2000-11-17 | 2001-11-15 | 내피세포 특이성을 나타내는 프로모터 및 이를 이용하는 방법 |
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US (1) | US20040048280A1 (ko) |
EP (3) | EP2386319B1 (ko) |
JP (1) | JP4243653B2 (ko) |
KR (2) | KR100917854B1 (ko) |
CN (1) | CN100457190C (ko) |
AT (1) | ATE455562T1 (ko) |
AU (2) | AU2400202A (ko) |
CA (1) | CA2429342C (ko) |
DE (1) | DE60141175D1 (ko) |
DK (2) | DK2186530T3 (ko) |
ES (2) | ES2425321T3 (ko) |
HK (3) | HK1068057A1 (ko) |
IL (1) | IL155940A0 (ko) |
MX (1) | MXPA03004325A (ko) |
PT (1) | PT2186530E (ko) |
WO (1) | WO2002040629A2 (ko) |
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US8039261B2 (en) * | 2000-11-17 | 2011-10-18 | Vascular Biogenics Ltd. | Promoters exhibiting endothelial cell specificity and methods of using same for regulation of angiogenesis |
AU2003222427B8 (en) | 2000-11-17 | 2010-04-29 | Vascular Biogenics Ltd. | Promoters exhibiting endothelial cell specificity and methods of using same |
US7067649B2 (en) * | 2000-11-17 | 2006-06-27 | Vascular Biogenics Ltd. | Promoters exhibiting endothelial cell specificity and methods of using same |
US8071740B2 (en) * | 2000-11-17 | 2011-12-06 | Vascular Biogenics Ltd. | Promoters exhibiting endothelial cell specificity and methods of using same for regulation of angiogenesis |
US20070286845A1 (en) * | 2000-11-17 | 2007-12-13 | Vascular Biogenics Ltd. | Promoters exhibiting endothelial cell specificity and methods of using same for regulation of angiogenesis |
US20100282634A1 (en) * | 2000-11-17 | 2010-11-11 | Dror Harats | Promoters Exhibiting Endothelial Cell Specificity and Methods of Using Same for Regulation of Angiogenesis |
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