Targeting an adenoviral gene vector to cytokine-activated vascular endothelium via E-selectin

被引：55

作者：

Harari, OA

Wickham, TJ

Stocker, CJ

Kovesdi, I

Segal, DM

Huehns, TY

Sarraf, C

Haskard, DO

机构：

[1] Natl Heart & Lung Inst, BHF, Cardiovasc Med Unit, London, England

[2] Univ London Imperial Coll Sci Technol & Med, Sch Med, Hammersmith Hosp, Dept Histopathol, London, England

[3] Genvec Inc, Rockville, MD USA

[4] NCI, Expt Immunol, Bethesda, MD 20892 USA

来源：

GENE THERAPY | 1999年 / 6卷 / 05期

基金：

英国惠康基金;

关键词：

gene therapy; adenovirus; inflammation; endothelium; E-selectin;

D O I：

10.1038/sj.gt.3300898

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have aimed at selective gene delivery to vascular endothelial cells (EC) at sites of inflammation, by targeting E-selectin, a surface adhesion molecule that is only expressed by activated EC. An anti-E-selectin mAb, 1.2B6, was complexed with the adenovirus vector AdZ.FLAG (expressing the FLAG peptide) by conjugating it to an anti-FLAG mAb. Gene transduction of cultured EC was increased 20-fold compared with AdZ.FLAG complexed with a control bsAb providing EC were activated by cytokines. The anti-E-selectin-complexed vector transduced 29 +/- 9% of intimal EC in segments of pig aorta cultured with cytokines ex vivo, compared with less than 0.1% transduced with the control construct (P < 0.05). This strategy could be developed to target endothelium in inflamation with genes capable of modifying the inflammatory response.

引用

页码：801 / 807

页数：7

共 50 条

[1] Isolation of a common receptor for coxsackie B viruses and adenoviruses 2 and 5 [J].