AAV5-CAG-Cre-2A-GFP

Recombinant adeno-associated viruses (AAVs) have become the vector of choice for many viral gene therapies due to their broad tissue tropism, ability to transduce both dividing and non-dividing cells, low pathogenicity and genotoxicity, and low immunogenicity. Recombinant adeno-associated viruses (rAAVs) are promising viral vectors for gene delivery applications. Hundreds of AAV genotypes have been sequenced from several mammalian species, and to date, 12 serotypes (AAV1 to AAV12) have been defined for human and non-human primate isolates.

Transgenes packaged in the prototypical human serotype AAV2 have been effective in correcting genetic diseases of the eye, brain, muscle, liver, and lung in animal models and have been successfully used to treat blindness and muscular dystrophy in humans. However, other serotypes have demonstrated improved gene delivery capabilities in certain tissues relative to AAV2 that are associated with the capsid sequence. For example, in studies packaging the same transgene, AAV5 was more effective than AAV2 in transducing neurons and lung tissue. At the apical surface of airway epithelial cells, AAV5 demonstrated 20-fold and 50-fold greater transduction capacity than AAV2 in vivo and in vitro, respectively, and was as effective as AAV8 in systemic expression of coagulation factor IX for the treatment of hemophilia. These observations have fueled efforts to develop AAV5 as a vector for the treatment of genetic diseases.