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

M. Cotten, E. Wagner, K. Zatloukal, S. Phillips, D. T. Curiel, M. L. Birnstiel

Research output: Contribution to journalArticle

292 Scopus citations

Abstract

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 β-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.

Original languageEnglish
Pages (from-to)6094-6098
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number13
DOIs
StatePublished - Jul 20 1992

Keywords

  • asialoglycoprotein
  • cosmid
  • endocytosis
  • gene therapy
  • transferrin

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