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.

作者：Matthew L. Cotten, Ernst Wagner, Kurt Zatloukal, S M Phillips, David T. Curiel, Max L. Birnstiel · 发表于：Proceedings of the National Academy of Sciences · 年份：1992 · DOI：10.1073/pnas.89.13.6094 · 被引用次数：318 · 研究领域：Virus-based gene therapy research、RNA Interference and Gene Delivery、Viral Infectious Diseases and Gene Expression in Insects

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, greater than 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.