In vivo gene delivery and expression by bacteriophage lambda vectors.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Lankes
H A
HA
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Zanghi
C N
CN
Santos
K
K
Capella
C
C
Duke
C M P
CM
Dewhurst
S
S
D000818:Animals; D010582:Bacteriophage lambda / Q000235:genetics*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D051379:Mice; D008807:Mice, Inbred BALB C / Q000382:microbiology; D014612:Vaccines
D014612:Vaccines