A collaboration between UniQure researchers and the University of Navarra has resulted in the successful expression of two transgenes in animal models following subsequent administration of the chimeric adeno associated virus (AAV) vectors AAV5ch and AAV1. This result is significant to the gene therapy field as it highlights two possible serotypes for re-administration of AAV in the event of a decline in therapeutic protein expression after the initial treatment.
In cases where the expression of a particular therapeutic gene has declined, re-administration cannot be carried out by the same AAV vector that was originally used due to the serotype-specific, anti-AAV neutralizing antibodies (NABs) that are produced after initial treatment. To investigate the feasibility of using a secondary, chimeric AAV vector, researchers created a corresponding model by immunizing animals with a high dose of AAV5ch-human secreted embryonic alkaline phosphatase (hSEAP) that generates high levels of anti-AAV5ch NAB. This was followed by a secondary and equivalent dose of AAV1-human factor IX (hFIX).
Results, which are published in the journal Molecular Therapy, showed successful expression of both reporter transgenes in the livers of non human primate, along with additional results that suggest causes for the decline in transgene expression over time.
Source: Successful Repeated Hepatic Gene Delivery in Mice and Non-human Primates Achieved by Sequential Administration of AAV5ch and AAV1. Majowicz A et al. Molecular Therapy June 2017. DOI