Lentivirus administration to rat muscle provides efficient sustained expression of erythropoietin

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Abstract
A lentivirus pseudotyped with vesicular stomatitis virus G protein (VSV-G) encoding rat erythropoietin (EPO) complementary DNA was administered to rat skeletal muscle and red blood cell production was serially monitored. After a single intramuscular injection hematocrit values increased and reached a plateau at about 35 days and were sustained for at least 14 months. Virus doses of 6 × 107infectious units and 6 × 106 infectious units produced significantly increased mean hematocrit values of 68.5% ± 2.1% (P < .001, n = 4) and 52.7% ± 1.3% (P < .001, n = 3), respectively, over values of control animals receiving normal saline (46.2% ± 1.5%, n = 2). A polymerase chain reaction (PCR) assay for vector sequences in genomic DNA showed muscle tissue at the site of injection was positive and undetectable in liver, spleen, kidney, and lung. The intramuscular administration of lentivirus provided a dose-responsive, highly efficient and sustained EPO gene delivery, suggesting these vectors may be applied generally to the systemic delivery of proteins such as hormones and clotting factors.