Novel compound enables high-level adenovirus transduction in the absence of an adenovirus-specific receptor

Christine M. Fouletier-Dilling, Pablo Bosch, Alan R. Davis, Jessica A. Shafer, Steven L. Stice, Zbigniew Gugala, Francis H. Gannon, Elizabeth A. Olmsted-Davis

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Viral vectors are extensively used to deliver foreign DNA to cells for applications ranging from basic research to potential clinical therapies. A limiting step in this process is virus uptake and internalization into the target cells, which is mediated by membrane receptors. Although it is possible to modify viral capsid proteins to target the viruses, such procedures are complex and often unsuccessful. Here we present a rapid, inexpensive system for improving transduction of cells, including those that lack receptors for adenovirus fiber proteins. Addition of GeneJammer (Stratagene, La Jolla, CA) during the adenovirus transduction led to a significant increase in both the total number of transduced cells and the level of transgene expression per cell. Studies using cell lines deficient in adenovirus receptors demonstrated that addition of GeneJammer provided a novel cellular entry mechanism for the virus. These findings were tested in a cell-based gene therapy system for the induction of bone, which is contingent on high-level expression of the transgene. Inclusion of GeneJammer in either Ad5BMP2 or Ad5F35BMP2 transduction of a variety of cells demonstrated a correlating increase in bone formation. The results suggest a novel and versatile method for achieving high-level transduction using adenovirus.

Original languageEnglish (US)
Pages (from-to)1287-1297
Number of pages11
JournalHuman Gene Therapy
Volume16
Issue number11
DOIs
StatePublished - Nov 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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