Determining the Minimally Effective Dose of a Clinical Candidate Adeno-Associated Virus Vector in a Mouse Model of Hemophilia A.

Hemophilia A, a bleeding disorder, affects 1:5,000 males and is caused by a deficiency of human blood coagulation factor VIII (hFVIII). Studies in mice and macaques identified AAVhu37.E03.

AAV8 Gene Therapy for Crigler-Najjar Syndrome in Macaques Elicited Transgene T Cell Responses That Are Resident to the Liver.

Systemic delivery of adeno-associated viral (AAV) vectors has been evaluated for the treatment of several liver diseases, including homozygous familial hypercholesterolemia, ornithine transcarbamylase deficiency, and hemophilia. Here, we evaluated this approach for the treatment of Crigler-Najjar syndrome. We administered wild-type rhesus macaques with 1.

Determining the Minimally Effective Dose of a Clinical Candidate AAV Vector in a Mouse Model of Crigler-Najjar Syndrome.

Liver metabolism disorders are attractive targets for gene therapy, because low vector doses can reverse the buildup of toxic metabolites in the blood. Crigler-Najjar syndrome is an inherited disorder of bilirubin metabolism that is caused by the absence of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) activity. This syndrome is characterized by hyperbilirubinemia and jaundice.