Correction of Hyperbilirubinemia in Gunn Rats by Surgical Delivery of Low Doses of Helper-Dependent Adenoviral Vectors

摘要: Abstract Helper-dependent adenoviral (HDAd) vectors are attractive for liver-directed gene therapy because they can drive sustained high levels of transgene expression without chronic toxicity. However, vector doses required to achieve efficient hepatic transduction by systemic delivery a nonlinear dose response. Unfortunately, such result in dissemination and dose-dependent acute toxicity with potential lethal consequences. We have previously shown nonhuman primates that HDAd surgically isolated livers resulted significantly higher reduced compared intravenous multiyear expression. Encouraged these data, we now employed surgical method the Gunn rat, an animal model Crigler–Najjar syndrome. After into liver, show phenotypic correction at low clinically relevant dos...