Current issues in adeno-associated viral vector production.

ABSTRACT

Adeno-associated virus (AAV) is currently one of the most promising systems for human gene therapy. Numerous preclinical studies have documented the excellent safety profile of these vectors along with their impressive performances in their favored target, consisting of highly differentiated postmitotic tissues such as muscle, central nervous system and liver. Clinical trials have been conducted confirming these data, but also emphasizing the requirement of further high-tech developments of the production and purification procedures that would allow both scaling-up and improvement of vector batch quality, necessary to human application. The scope of this review will be the state of the art in the various production methods of recombinant AAV (rAAV), delimiting their respective perimeter of application and also their main advantages and drawbacks, and thereby shedding light on the main challenges to take in the near future to bring AAV vectors more widely into the clinics.