Erythropoietin gene therapy leads to autoimmune anemia in macaques

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 supra-physiologic 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 autoimmunity in primates. (C) 2004 by The American Society of Hematology.