An all-feline retroviral packaging system for transduction of human cells.

Publication Type:

Journal Article

Source:

Human gene therapy, Volume 21, Issue 8, p.1019-27 (2010)

Keywords:

2010, Animals, Antigens, CD34, Cats, Center-Authored Paper, Gene Therapy, Gene Transfer Techniques, Genetic Vectors, Hematopoietic Stem Cells, Human Biology Division, Humans, Leukemia Virus, Feline, Membrane Transport Proteins, Receptors, Virus, Transduction, Genetic

Abstract:

Abstract The subgroup C feline leukemia virus (FeLV-C) receptor FLVCR is a widely expressed 12-transmembrane domain transporter that exports cytoplasmic heme and is a promising target for retrovirus-mediated gene delivery. Previous studies demonstrated that FeLV-C pseudotype vectors were more efficient at targeting human hematopoietic stem cells than those pseudotyped with gibbon ape leukemia virus (GALV), and thus we developed an all FeLV-C-based packaging system, termed CatPac. CatPac is helper-virus free and can produce higher titer vectors than existing gammaretroviral packaging systems, including systems mixing Moloney murine leukemia virus (MoMLV) Gag-Pol and FeLV-C Env proteins. The vectors can be readily concentrated (>30-fold), refrozen (three to five times), and held on ice (>2 days) with little loss of titer. Furthermore, we demonstrate that CatPac pseudotype vectors efficiently target early CD34(+)CD38(-) stem/progenitor cells, monocytic and erythroid progenitors, activated T cells, mature macrophages, and cancer cell lines, suggesting utility for human cell and cell line transduction and possibly gene therapy.