High-efficiency gene transfer mediated by adenovirus coupled to DNA-polylysine complexes

David T. Curiel, Ernst Wagner, Matt Gotten, Max L. Birnstiel, Santosh Agarwal, L. I. Cheng-Ming, Steve Loechel, Ping Chuan Hu

Research output: Contribution to journalArticlepeer-review

212 Scopus citations

Abstract

Employment of recombinant viruses as gene transfer vectors is limited by constraints on the size and functional design of the genetic material to be transferred as well as potential safety hazards deriving from obligatory co-transfer of viral genetic elements. As an alternative strategy that capitalizes on the efficient cellular entry mechanisms of viruses, we have derived adenovirus-polylysine-DNA complexes whereby foreign DNA is transferred bound to the exterior of the virion. This linkage was accomplished utilizing an antibody bridge in which a monoclonal antibody was rendered competent to carry DNA by the attachment of a poly lysine residue. Attachment of the antibody-polylysine to the virus was by virtue of the antibody's specificity for the virion. The resulting vector system mediates high-efficiency gene transfer to target cells in vitro. In addition, this vector design allows greatly enhanced flexibility in terms of the size and design of heterologous sequences that can be transferred. Since this strategy selectively exploits viral entry functions, which are independent of viral gene expression, the potential exists to derive vectors that avoid the hazards deriving from transfer of parent virus genome.

Original languageEnglish
Pages (from-to)147-154
Number of pages8
JournalHuman Gene Therapy
Volume3
Issue number2
DOIs
StatePublished - 1992

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