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 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
Guangping
G
Gene Therapy Program, Division of Medical Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Lebherz
Corinna
C
Weiner
Daniel J
DJ
Grant
Rebecca
R
Calcedo
Roberto
R
McCullough
Beth
B
Bagg
Adam
A
Zhang
Yi
Y
Wilson
James M
JM
D000744:Anemia, Hemolytic, Autoimmune / Q000139:chemically induced*; D000818:Animals; D015551:Autoimmunity; D000229:Dependovirus / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D004921:Erythropoietin / Q000009:adverse effects* / Q000235:genetics / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000009:adverse effects* / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects; D008251:Macaca; D011086:Polycythemia / Q000139:chemically induced; D019076:Transgenes
D004921:Erythropoietin