Feline immunodeficiency virus vectors for efficient transduction of primary human synoviocytes: application to an original model of rheumatoid arthritis.

Abstract

The potential of gene therapeutics is hindered by the limitations of the delivery systems presently available. Recently, human immunodeficiency virus (HIV) vectors have been developed that allow the efficient and stable transduction of primary nondividing cells in vivo. Because of the safety concerns raised by HIV vectors, we developed a gene delivery system derived from the ungulate lentivirus feline immunodeficiency virus (FIV). We describe in the present study the optimization of the safety and efficiency of this system that proved to be as potent as HIV vectors to transduce nondividing cells, with titers over 10(8) transducing units per ml. We used this tool to transduce TNF-alpha into human primary synoviocytes, and showed a high efficiency of transduction. TNF-alpha-transduced synoviocytes injected into the knee joints of severe combined immunodeficient (SCID) mice induced cell proliferation, as well as cartilage and bone erosion as soon as day 7, creating a standardized, humanized animal model relevant for rheumatoid arthritis. FIV vectors appear to be promising tools for biologic research and gene therapy.