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

ABSTRACT: 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 1.0 × 10¹³ or 2.5 × 10¹³ genome copies/kg of an AAV serotype 8 vector expressing a codon-optimized version of human uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) from a liver-specific promoter. We extensively studied vector biodistribution, transgene expression, and immune responses following vector administration. All rhesus macaques survived until their scheduled necropsy at day 56 and showed no clinical a

SUBMITTER: Greig JA 

PROVIDER: S-EPMC6282099 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature