Efficiency ofIn VivoGene Transfer Using Murine Retroviral Vectors Is Strain-Dependent in Mice

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Abstract
Retroviral vectors can be used to transduce cultured cells at high frequencies, but efficient transduction of target cells in vivo has proved difficult and little is known about the factors that influence the efficiency of retroviral infection. Many commonly used mouse strains harbor endogenous C-type proviruses, some of which are expressed and have circulating antibodies against the viral envelope glycoproteins that cross-react with the Moloney strain of murine leukemia virus (MoMLV), from which most current retroviral vectors are derived. We have investigated the relative efficiency of retroviral-mediated gene transfer into regenerating skeletal muscle of a variety of mouse strains using a MoMLV-based vector. Humoral immune competence and interference between endogenous MLVs and exogenous recombinant MoMLV were observed to affect the efficiency of retroviral-mediated transfection in vivo. Our results indicate that the mouse genetic background and immune status need to be considered when choosing a preclinical model for in vivo retroviral-mediated gene transfer. Moloney murine leukemia virus (MoMLV)-based retroviral vectors have been used to transfer, integrate, and express foreign genes efficiently in a wide variety of mammalian cells in vitro. However, only moderate efficiency has been obtained by direct in vivo administration of recombinant retrovirus. Fassati et al. have found that the efficiency of infection in vivo by ecotropic MoMLV-based vectors is reduced in many commonly used mouse strains that express antibodies against endogenous retroviruses. The genetic background and immune status need to be considered when choosing a mouse model for retrovirus-mediated gene therapy.