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 tested for its potential to confer long-term expression the gene product following intramuscular injection. A intramuscular injection of 2 x 10(12) rAAV-cm-Epo particles two baboons led to sustained high circulating and a concomitant increase in hematocrit. The hematocrits reached 62 and 75% by week 10 (from preinjection 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.