Adeno-associated virus-mediated delivery of erythropoietin leads to sustained elevation of hematocrit in nonhuman primates.
Recombinant adeno-associated virus encoding the monkey erythropoietin gene (rAAV-cm-Epo) was generated and tested for its potential to confer long-term expression of the gene product following intramuscular injection. A single intramuscular injection of 2 x 10(12) rAAV-cm-Epo particles into two baboons led to sustained high circulating Epo levels and a concomitant increase in hematocrit. The hematocrits reached 62 and 75% by week 10 (from pre-injection values of 38 and 40%, respectively) and remained elevated throughout the study period (28 weeks). Circulating Epo levels were also elevated throughout the study period. Our data demonstrate the potential for long-term gene expression in large animals by a single intramuscular injection of a recombinant adeno-associated virus (rAAV) vector.
Zhou
S
S
Chiron Corporation, Emeryville, CA, USA.
Murphy
J E
JE
Escobedo
J A
JA
Dwarki
V J
VJ
D000818:Animals; D000906:Antibodies / Q000032:analysis; D000229:Dependovirus / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000097:blood / Q000235:genetics*; D005354:Fibrosarcoma; D018014:Gene Transfer Techniques; D006400:Hematocrit; D006801:Humans; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010215:Papio / Q000276:immunology; D011994:Recombinant Proteins / Q000097:blood; D013997:Time Factors
D000906:Antibodies; D011994:Recombinant Proteins; D004921:Erythropoietin