Intégration des vecteurs AAV et mutagenèse insertionnelle

Abstract

Recombinant AAV vectors (rAAV) are considered as very efficient tools for in vivo gene transfer. Accordingly, several preclinical and clinical gene therapy trials use these vectors to treat inherited and acquired diseases. rAAV vectors possess the capacity to persist for a long term in the transduced tissue in a transcriptionally active, extra-chromosomal (episomal) form. However, many studies have shown that a significant fraction of the rAAV genomes can also nonspecifically integrate into the host cell genome thus raising the possibility of insertional mutagenesis events. This review summarizes the current knowledge on integration of wild type and rAAV genomes and highlights the major questions which remain unresolved.