Intramuscular delivery of erythropoietin via AAV vectors in macaques led to supraphysiologic EPO levels and polycythemia, followed by severe autoimmune anemia in some animals.
Does intramuscular AAV-mediated EPO gene therapy cause autoimmune anemia in cynomolgus macaques?
Intramuscular AAV-mediated EPO gene therapy in macaques can lead to inadvertent autoimmunity and severe anemia, highlighting a critical safety concern for gene therapy in primates.
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.
Gao et al. (Mon,) reported a other. Erythropoietin (EPO) gene therapy via AAV vectors was evaluated on Development of polycythemia and autoimmune anemia. Intramuscular delivery of erythropoietin via AAV vectors in macaques led to supraphysiologic EPO levels and polycythemia, followed by severe autoimmune anemia in some animals.