Published online Aug 27, 2015. doi: 10.5496/wjmg.v5.i3.28
Peer-review started: January 8, 2015
First decision: February 6, 2015
Revised: May 11, 2015
Accepted: May 16, 2015
Article in press: May 18, 2015
Published online: August 27, 2015
Adeno-associated virus (AAV) is a small, non-enveloped virus that contains a single-stranded DNA genome. It was the first gene therapy drug approved in the Western world in November 2012 to treat patients with lipoprotein lipase deficiency. AAV made history and put human gene therapy in the forefront again. More than four decades of research on AAV vector biology and human gene therapy has generated a huge amount of valuable information. Over 100 AAV serotypes and variants have been isolated and at least partially characterized. A number of them have been used for preclinical studies in a variety of animal models. Several AAV vector production platforms, especially the baculovirus-based system have been established for commercial-scale AAV vector production. AAV purification technologies such as density gradient centrifugation, column chromatography, or a combination, have been well developed. More than 117 clinical trials have been conducted with AAV vectors. Although there are still challenges down the road, such as cross-species variation in vector tissue tropism and gene transfer efficiency, pre-existing humoral immunity to AAV capsids and vector dose-dependent toxicity in patients, the gene therapy community is forging ahead with cautious optimism. In this review I will focus on the properties and applications of commonly used AAV serotypes and variants, and the technologies for AAV vector production and purification. I will also discuss the advancement of several promising gene therapy clinical trials.
Core tip: Adeno-associated virus (AAV) has become the first gene therapy drug approved by the Western world and spurred huge excitement in the gene therapy field. The gene therapy community is forging ahead with cautious optimism despite some challenges down the road. A battery of more than 100 AAV serotypes and variants are available and AAV production and purification technologies have become well established. Several clinical trials with AAV vectors have yielded exciting results. This paper will give you the information needed to understand the current development of the gene therapy field with AAV vectors.