Feline immunodeficiency virus vectors for efficient transduction of primary human synoviocytes: application to an original model of rheumatoid arthritis.
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.
Lin
Yea-Lih
YL
Institut de Génétique Humaine, CNRS UPR1142, 34396 Montpellier Cedex 5, France.
Noël
Danièle
D
Mettling
Clément
C
Réant
Brigitte
B
Clot
Jacques
J
Jorgensen
Christian
C
Corbeau
Pierre
P
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000628:therapy; D001842:Bone and Bones; D002356:Cartilage; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005822:Genetic Vectors; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000235:genetics*; D051379:Mice; D016513:Mice, SCID; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha