Systemic Administration of Feline Immunodeficiency Virus as a Basis for Global Gene Therapy

Objective: Defective, VSV-G pseudotyped, feline immunodeficiency virus (FIV) vectors have been previously shown to successfully transduce dividing, growth arrested as well as post-mitotic cells. The aim of this study was to characterize the distribution of FIV and correlate transgene expression in vital organs of young adult and neonatal mice following systemic administration. Methods: FIV viral solutions were prepared in vitro and titered in feline kidney fibroblasts (CrfK). Young adult mice (3 months old) were injected with increasing doses of virus (dose response) and were sacrificed 5 weeks following treatment. In addition, neonatal mice (4 days old) were injected also intraperitoneally and were sacrificed at 3, 6 and 13 weeks post-treatment (time response). Transgene expression was assessed by histochemical, enzymatic and immunocytochemical methods of analysis. Results: (1) Increasing FIV doses of administration resulted in elevated transgene expression in a dose response manner. (2) Transgene expression increased with time, the levels of which appeared to plateau at 13 weeks; (3) Cells of the liver, spleen and brain appeared to be successfully transduced by FIV. (4) A considerable immune response was observed in the adult animals compared to the neonates following systemic FIV administration. Conclusions: The wide distribution and stable transgene expression obtained after FIV systemic administration suggests it can become the basis of global gene therapy. Supported in part by NIH/NIDCR DE00471 and DE13860, and the American Association of Orthodontists Foundation.