AAV Vector Delivery to Cells in Culture

Adeno-associated virus (AAV) gene delivery vectors are being investigated as vehicles for gene therapy for a wide variety of hereditary and acquired human diseases. AAV’s inability to self-propagate, ability to be maintained as an episome in the transduced cell, and relatively innocuous effects on the immune system make it the vector of choice for prolonged in vivo gene expression. AAV type 2 is the most commonly used serotype for gene delivery. AAV2 vectors will deliver DNA to a wide variety of cell types. The development of vectors derived from the other five serotypes has expanded the tissue tropism of the AAV vector system (1 –6 ). Tropism depends on the presence of cell-surface receptor elements on the target cell. For AAV2, heparin sulfate proteoglycan (7 ), α₂ β_V integrin (8 ) and the fibroblast growth factor receptor-1 (FGFR-1) (9 ) are believed to mediate the initial internalization steps in infection. The ubiquity of these cell-surface components confers a wide tropism on AAV2 vectors.