AAV6-CMV-Luc

Adeno-associated virus (AAV), originally discovered in 1965 as a contaminant of adenovirus preparations, has become one of the most extensively studied viral gene therapy vectors in the world over the past 50 years or so. There are currently three FDA-approved AAV vector-derived therapies available for the treatment of genetic diseases. AAV is considered a revolutionary target for gene therapy, with the potential to address a wide range of genetic diseases. Their natural tropism for human cells, ability to infect both non-dividing and dividing cells, and minimal immunogenicity are great advantages for the use of AAV vectors. This, coupled with a small genome that can be easily modified to carry therapeutic transgenes and to express transgenes sustainably in cells, further expands the potential of AAV as a gene therapy vector. AAV, belonging to the Parvoviridae family and the Dependoparvovirus genus, is a small (~4.7 kb), single-stranded DNA virus containing three genes (rep, cap, and aap) flanked by inverted terminal repeats. There are at least 12 serotypes of AAV isolated from human and primate tissues, with more than 150 different serotype variants. AAV serotype 6 (AAV6) is considered a hybrid recombinant of AAV serotype 1 and AAV serotype 2. However, it has retained its serotype number due to differences in the transduction profiles of the serotypes. This is suspected to be due to differences in the cellular uptake and intracellular trafficking mechanisms of AAV serotype vectors, particularly structural differences at the capsid level. Currently, AAV6 has been shown to transduce lymphocytes and has been used to generate chimeric antigen receptor T cells for immunotherapy.