Impact of intravenous infusion time on AAV8 vector pharmacokinetics, safety, and liver transduction in cynomolgus macaques.

ABSTRACT: Systemically delivered adeno-associated viral (AAV) vectors are now in early-phase clinical trials for a variety of diseases. While there is a general consensus on inclusion and exclusion criteria for each of these trials, the conditions under which vectors are infused vary significantly. In this study, we evaluated the impact of intravenous infusion rate of AAV8 vector in cynomolgus macaques on transgene expression, vector clearance from the circulation, and potential activation of the innate immune system. The dose of AAV8 vector in terms of genome copies per kilogram body weight and its concentration were fixed, while the rate of infusion varied to deliver the entire dose over different time periods, including 1, 10, or 90 minutes. Analyses during the in-life phase of the experiment inc

SUBMITTER: Greig JA 

PROVIDER: S-EPMC5142508 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature