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Blood, 1 August 2001, Vol. 98, No. 3, pp. 594-596
GENE THERAPY
Lentivirus administration to rat muscle provides efficient
sustained expression of erythropoietin
Jurgen Seppen,
Simon C. Barry,
Brandon Harder, and
William R. A. Osborne
From the Department of Pediatrics, University of
Washington School of Medicine, Seattle, WA.
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 × 107
infectious 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.

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