AAV2-EF1a-mCherry

The use of recombinant adeno-associated virus (rAAV) vectors in clinical gene therapy has become widespread, primarily because rAAV vectors have demonstrated long-term transgene expression in animal models with minimal associated toxicity and an overall favorable safety profile in preclinical and clinical trials. Most early AAV gene therapy studies were conducted with serotype 2 vectors, but vector systems based on other AAV serotypes that have more efficient gene delivery and different tissue specificities are currently in human trials, and their use is likely to increase.

The ability to transduce different cell types is primarily determined by the AAV protein capsid. Different capsids bind to different cellular receptors, and this binding mediates entry into the cell. The primary receptor for AAV2 and AAV3 is heparan sulfate-proteoglycan. Integrin α5β5, integrin α5β1, hepatocyte growth factor receptor (c-Met), and CD9 have also been previously described as potential coreceptors for AAV2. Fibroblast growth factor receptor-1 is a co-receptor for AAV2 and AAV3, while the 37/67-kDa laminin receptor is a co-receptor for AAV2, AAV3, AAV8, and AAV9. The primary receptor for AAV1, AAV4, and AAV5 is O-linked sialic acid, while the primary receptor for AAV6 is N-linked sialic acid. Platelet-derived growth factor receptor is a co-receptor for AAV5. The differences in the cellular receptors to which the capsid binds result in each of these native AAV serotypes transducing a different range of cell types.