A Highly Efficient Gene Delivery System Derived from Feline Immunodeficiency Virus (FIV)

Feline immunodeficiency virus (FIV) is an appealing candidate for viral vector development because recombinant FIV vectors efficiently transduce dividing and nondividing cells and thus provides an alternative to primate lentiviral vectors derived from simian immunodeficiency virus (SIV) or human immunodeficiency virus (HIV). FIV naturally infects diverse Felidae worldwide and feline gene therapy vectors are equipped with human-tropic envelopes and hybrid long terminal repeats (LTRs), to overcome FIV’s cat-specific tropism and low activity of the FIV LTR in human cells, respectively. The simple genome organization of FIV with only three accessory/regulatory proteins facilitates vector development. Recombinant FIV vectors generate titers comparable to other lentiviral systems, and accessory proteins are not needed for high titer or efficient transduction. Compared to HIV vectors, FIV vector development is still in its infancy, but initial in vivo data in various species and tissues indicate long-term gene expression at therapeutic levels, and, therefore, FIV vectors hold great promise for gene therapy applications. Before we describe the generation of high-titer, replication-incompetent feline gene delivery systems, we will briefly discuss FIV biology and genome organization to highlight the questions that needed to be addressed during vector development.