Efficient transduction of pigtailed macaque hematopoietic repopulating cells with HIV-based lentiviral vectors

摘要: Lentiviral vectors are attractive for hematopoietic stem cell (HSC) gene therapy because they do not require mitosis nuclear entry, efficiently transduce repopulating cells, and self-inactivating (SIN) designs can be produced at high titer. Experiments to evaluate HIV-derived lentiviral in nonhuman primates prior clinical trials have been hampered by low transduction frequencies due part host restriction TRIM5α. We established conditions efficient of pigtailed macaque (Macaca nemestrina) long-term cells using VSV-G–pseudotyped HIV-based vectors. Stable, long-term, high-level marking was observed 3 macaques relatively MOIs (5-10) a 48-hour ex vivo protocol. All animals studied had rapid neutrophil engraftment with median 10.3 days count greater than 0.5 × 109/L (500/μL). Expression detected all lineages, levels granulocytes approximately 20% 30%, lymphocytes 12% 23%. polyclonal as determined analysis vector integration sites. These data suggest that should highly effective HSC therapy, particularly diseases which maintaining the potential short-term protocols is critical.