- Paper Report
- Open Access
Lentivirus-mediated expression following intramuscular injection
- Elvire Gouze1
© Biomed Central Ltd 2001
- Received: 15 August 2001
- Accepted: 4 October 2001
- Published: 4 October 2001
- gene therapy
HIV-1-based lentiviral vectors have the advantage over oncoretrovirus of enabling provirus integration into nondividing cells. These vectors successfully transduce a variety of human cells including muscle cells. Lentiviral vectors are often pseudotyped with vesicular stomatitis virus G (VSV-G) coat protein increasing their host cell range and allowing their concentration by ultracentrifugation.
Recombinant erythropoietin (EPO) has been widely used for treatments of anemia associated with chronic renal failure, cancer chemotherapy, and HIV infections. Persistent delivery of EPO by gene transfer rather than repeat injections would provide clinical and economic benefits. The authors investigated whether a self-inactivating lentiviral vector encoding rat EPO was able to mediate long-term expression after a single administration to rat muscle.
VSV-G pseudotyped, lentiviral vector encoding rat EPO was administered to rat skeletal muscle. Following a single intramuscular injection of lentivirus encoding EPO, the hematocrit levels increased in a dose-dependent manner reaching a plateau at 35 days that was maintained for at least 14 months. Following the injection of a plasmid containing the same coding sequence, hematocrit levels were not increased. The authors confirm the presence of the vector sequences in genomic DNA by PCR analysis of muscle tissues. No viral sequences were recovered in liver, spleen, kidney and lung. These data show that VSV-G pseudotype, lentiviral vectors can mediate long-term transgene expression after single administration to rat muscle.
Lentivirus production, hematocrit, PCR