title: Erythropoietin gene therapy leads to autoimmune anemia in macaques.
abstract: 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.
authors.affiliation: Gene Therapy Program, Division of Medical Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Guangping
authors.initials: G
authors.lastname: Gao
authors.forename: Corinna
authors.initials: C
authors.lastname: Lebherz
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weiner
authors.forename: Rebecca
authors.initials: R
authors.lastname: Grant
authors.forename: Roberto
authors.initials: R
authors.lastname: Calcedo
authors.forename: Beth
authors.initials: B
authors.lastname: McCullough
authors.forename: Adam
authors.initials: A
authors.lastname: Bagg
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: James M
authors.initials: JM
authors.lastname: Wilson
mesh_terms: 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
chemical_list: D004921:Erythropoietin