Journal
GENE THERAPY
Volume 17, Issue 10, Pages 1288-1293Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2010.75
Keywords
transduction; stable transformation; viral vector; eukaryotic plasmid
Categories
Funding
- USPHS [R37 CA025235]
- Ruth L Kirchstein National Research Service Award [GM007185]
- SDG [T32-GM07104]
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Epstein-Barr virus (EBV) evolved an episomal system for maintaining life-long, latent infection of human B lymphocytes. Circular episomes engineered from EBV components required for this latent form of infection have the capacity to persist in most types of replicating mammalian cells without DNA integration and the pitfalls of insertional mutagenesis. EBV episomes are typically transduced using low-efficiency methods. Here we present a method for efficient delivery of EBV episomes to nuclei of hepatocytes in living mice using a helper-dependent adenoviral vector and Cre-mediated recombination in vivo to generate circular EBV episomes following infection. Cre is transiently expressed from a hepatocyte-specific promoter so that vector generation and transgene expression are tissue specific. We show long-term persistence of the circularized vector DNA and expression of a reporter gene in hepatocytes of immunocompetent mice. Gene Therapy (2010) 17, 1288-1293; doi:10.1038/gt.2010.75; published online 13 May 2010
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