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J Appl Microbiol. 2007 May;102(5):1337-49.

In vivo gene delivery and expression by bacteriophage lambda vectors.

Author information

  • 1Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.

Abstract

AIMS:

Bacteriophage vectors have potential as gene transfer and vaccine delivery vectors because of their low cost, safety and physical stability. However, little is known concerning phage-mediated gene transfer in mammalian hosts. We therefore performed experiments to examine phage-mediated gene transfer in vivo.

METHODS AND RESULTS:

Mice were inoculated with recombinant lambda phage containing a mammalian expression cassette encoding firefly luciferase (luc). Efficient, dose-dependent in vivo luc expression was detected, which peaked within 24 h of delivery and declined to undetectable levels within a week. Display of an integrin-binding peptide increased cellular internalization of phage in vitro and enhanced phage-mediated gene transfer in vivo. Finally, in vivo depletion of phagocytic cells using clodronate liposomes had only a minor effect on the efficiency of phage-mediated gene transfer.

CONCLUSIONS:

Unmodified lambda phage particles are capable of transducing mammalian cells in vivo, and may be taken up -- at least in part -- by nonphagocytic mechanisms. Surface modifications that enhance phage uptake result in more efficient in vivo gene transfer.

SIGNIFICANCE AND IMPACT OF THE STUDY:

These experiments shed light on the mechanisms involved in phage-mediated gene transfer in vivo, and suggest new approaches that may enhance the efficiency of this process.

PMID:
17448169
[PubMed - indexed for MEDLINE]
PMCID:
PMC2063594
Free PMC Article

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