Correction of hyperbilirubinemia in gunn rats using clinically relevant low doses of helper-dependent adenoviral vectors.

ABSTRACT: Crigler-Najjar syndrome type I is a severe inborn error of bilirubin metabolism caused by a complete deficiency of uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) and results in life-threatening unconjugated hyperbilirubinemia. Lifelong correction of hyperbilirubinemia by liver-directed gene therapy using a helper-dependent adenoviral (HDAd) vector has been previously reported in the Gunn rat, a model of Crigler-Najjar syndrome, but was only achieved using high doses (≥ 3 × 10(12) viral particles [vp]/kg), which are likely to elicit a severe toxic response in humans. Therefore, in this study, we investigate strategies to achieve correction of hyperbilirubinemia in the Gunn rat using clinically relevant low HDAd doses. We have found that correction of hyperbilirubinemia in the Gunn

SUBMITTER: Dimmock D 

PROVIDER: S-EPMC3073075 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature