Successful Repeated Hepatic Gene Delivery in Mice and Non-human Primates Achieved by Sequential Administration of AAV5^ch and AAV1.

ABSTRACT: In the gene therapy field, re-administration of adeno-associated virus (AAV) is an important topic because a decrease in therapeutic protein expression might occur over time. However, an efficient re-administration with the same AAV serotype is impossible due to serotype-specific, anti-AAV neutralizing antibodies (NABs) that are produced after initial AAV treatment. To address this issue, we explored the feasibility of using chimeric AAV serotype 5 (AAV5^ch) and AAV1 for repeated liver-targeted gene delivery. To develop a relevant model, we immunized animals with a high dose of AAV5^ch-human secreted embryonic alkaline phosphatase (hSEAP) that generates high levels of anti-AAV5^ch NAB. Secondary liver transduction with the same dose of AAV1-human factor IX (hF

SUBMITTER: Majowicz A 

PROVIDER: S-EPMC5542767 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature