Progress in adeno-associated virus type 2 vector production: promises and prospects for clinical use.

Abstract

Vectors derived from the human parvovirus AAV-2 (adeno-associated virus type 2) are among the most promising gene delivery vehicles currently being developed. These vectors are not only capable of transducing a large variety of human cell types in vitro and in vivo, but in immunocompetent animal models can establish long-term gene expression without being pathogenic to the recipient. However, a limitation of this vector system with respect to its clinical application has long been the laborious work needed to prepare high-titer and pure AAV-2 vector stocks. A number of improvements to the basic manufacturing protocol have recently been reported that now allow the production of AAV-2 vectors of significantly higher quality and quantity. This article considers the most relevant approaches taken so far, which include modifications to the conventional transfection/infection protocol as well as the development of helper virus-free packaging methods and the establishment of vector producer cell lines. The various novel protocols are discussed, including their advantages and drawbacks, with a particular focus being put on their prospects for clinical use. Despite these advancements, the development of an ideal AAV-2 vector production method fully suiting clinical requirements obviously remains a challenging issue.