AAV6-CAG-Cre-GFP

Over the past few years, adeno-associated virus (AAV) vectors have gained increasing attention as gene delivery vehicles for preclinical studies and are increasingly being used in clinical trials to treat a wide range of diseases. In addition, treatment of lipoprotein lipase deficiency with AAV vectors was the first gene therapy to receive clinical approval in the Western world. The most attractive features of AAV vectors include the lack of pathogenicity of wild-type AAV, multiple serotypes with broad but different tropisms, and low immunogenicity of AAV. Twelve AAV serotypes and numerous variants from humans and non-human primates have been identified, with different serological characteristics, cell surface receptor usage, and tissue tropism. Serotypes can be broadly divided based on their primary cell surface receptor usage: AAV2, -3, and -6 bind heparan sulfate proteoglycans (HSPGs), AAV1, -4, -5, and -6 bind sialic acid, and AAV9 binds galactose. The coreceptors for internalization also vary and include laminin receptors, epidermal growth factor receptor, hepatocyte growth factor receptor, platelet-derived growth factor receptor, and several integrins. A recently discovered novel receptor, AAVR, appears to be required for infection by some variants. Most serotypes rely on AAVR for successful cellular internalization but bind and interact with it differently. Exceptions include AAV4 and the chimeric variant AAVrh32.33, which use an AAVR-independent pathway.