Long-term erythropoietin expression in rodents and non-human primates following intramuscular injection of a replication-defective adenoviral vector

Hum Gene Ther. 1997 Oct 10;8(15):1797-806. doi: 10.1089/hum.1997.8.15-1797.


Erythropoietin (Epo)-responsive anemia is a debilitating complication of chronic renal failure and human immunodeficiency virus (HIV) infection that effects more than 150,000 Americans. Patients with Epo-responsive anemias are currently treated with repeated injections of recombinant human Epo. In the studies described in this report, we have examined the safety and efficacy of using a single intramuscular (i.m.) injection of replication-defective adenoviral vectors (RDAd) encoding Epo for the treatment of Epo-responsive anemias in both mice and non-human primates. Our results demonstrate that there is a threshold dose of virus (2.5-8 x 10(7) pfu/gram of body weight) which is required to obtain long-term Epo expression and polycythemia in both species. A single i.m. injection of mice with 10(9) pfu of an RDAd encoding murine Epo (AdmEpo) resulted in elevations in hematocrits from control values of 49 +/- 0.9% to treated values of 81 +/- 3%, which were stable for more than 1 year. Similarly, a single i.m. injection of a monkey with 4 x 10(11) pfu of an RDAd-encoding simian Epo (AdsEpo) resulted in elevations of hematocrits from control levels of 40% to treated levels of > or =70%, which were stable for 84 days. Intramuscular injection of monkeys with AdsEpo appeared to be safe in that we did not detect abnormalities in chest X-rays, serum chemistries, hematologic, or clotting profiles (apart from elevated hematocrits) or organ histologies during the 84-day time course of the experiment. Taken together, these results suggest the feasibility of using i.m. injection of RDAd for the treatment of Epo-responsive anemias in humans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics*
  • Anemia / therapy*
  • Animals
  • Antibodies, Viral / blood
  • Defective Viruses*
  • Dose-Response Relationship, Drug
  • Erythropoietin / biosynthesis
  • Erythropoietin / genetics*
  • Erythropoietin / therapeutic use
  • Feasibility Studies
  • Gene Expression
  • Gene Transfer Techniques*
  • Genetic Therapy*
  • Genetic Vectors*
  • Hematocrit
  • Injections, Intramuscular
  • Macaca fascicularis
  • Mice
  • Rodentia
  • Time Factors
  • Virus Replication


  • Antibodies, Viral
  • Erythropoietin