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

Vectors derived from the human parvovirus AAV-2 (adeno-associated virus typ e 2) are among the most promising gene delivery vehicles currently being de veloped. These vectors are not only capable of transducing a large variety of human cell types in vitro and in vivo, but in immunocompetent animal mod els can establish longterm 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 hig h-titer and pure AAV-2 vector stocks. A number of improvements to the basic manufacturing protocol have recently been reported that now allow the prod uction 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 a s the development of helper virus-free packaging methods and the establishm ent of vector producer cell lines. The various novel protocols are discusse d, including their advantages and drawbacks, with a particular focus being put on their prospects for clinical use. Despite these advancements, the de velopment of an ideal AAV-2 vector production method fully suiting clinical requirements obviously remains a challenging issue.