Erythropoietin gene therapy leads to autoimmune anemia in macaques

Blood. 2004 May 1;103(9):3300-2. doi: 10.1182/blood-2003-11-3852. Epub 2003 Dec 24.


Gene therapy is being considered for the delivery of therapeutic proteins. We evaluated the delivery of the hormone erythropoietin (EPO) into cynomolgus macaques through intramuscularly administered adeno-associated virus (AAV) vectors. As expected, the animals developed supraphysiologic levels of EPO and polycythemia. However, severe anemia ensued in some animals because of an autoimmune response to endogenous and transgene derived EPO. This is the first example of gene therapy leading to inadvertent auto-immunity in primates.

Publication types

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

MeSH terms

  • Anemia, Hemolytic, Autoimmune / chemically induced*
  • Animals
  • Autoimmunity
  • Dependovirus / genetics
  • Drug Evaluation, Preclinical
  • Erythropoietin / adverse effects*
  • Erythropoietin / genetics
  • Erythropoietin / therapeutic use*
  • Genetic Therapy / adverse effects*
  • Genetic Therapy / methods
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / adverse effects
  • Macaca
  • Polycythemia / chemically induced
  • Transgenes


  • Erythropoietin