HIGH-EFFICIENCY RECEPTOR-MEDIATED DELIVERY OF SMALL AND LARGE (48 KILOBASE GENE CONSTRUCTS USING THE ENDOSOME-DISRUPTION ACTIVITY OF DEFECTIVE OR CHEMICALLY INACTIVATED ADENOVIRUS PARTICLES

被引:305
作者
COTTEN, M [1 ]
WAGNER, E [1 ]
ZATLOUKAL, K [1 ]
PHILLIPS, S [1 ]
CURIEL, DT [1 ]
BIRNSTIEL, ML [1 ]
机构
[1] UNIV N CAROLINA, CHAPEL HILL, NC 27599 USA
关键词
GENE THERAPY; ENDOCYTOSIS; TRANSFERRIN; ASIALOGLYCOPROTEIN; COSMID;
D O I
10.1073/pnas.89.13.6094
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
One limit to successful receptor-mediated gene delivery is the exit of the endocytosed material from the endosome. We demonstrate here the delivery of marker genes to tissue culture cells using a modification of the receptor-mediated gene delivery technique that exploits the endosomolytic activity of defective adenovirus particles. In particular, >90% of the transfected-cell population is found to express a beta-galactosidase gene, and, most importantly, this high level of expression can be obtained with psoralen-inactivated virus particles. Furthermore, because the delivered gene is not carried within the genome of the adenovirus particle, the size constraints are relieved, and we can, therefore, show the delivery of a 48-kilobase cosmid DNA molecule.
引用
收藏
页码:6094 / 6098
页数:5
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