CAG-FLEX-NES-jRCaMP1a AAV (Serotype 8)

Adeno-associated viruses (AAV) are a promising gene delivery vector system. They are small (~26 nm), non-enveloped viruses belonging to the Parvoviridae family, have a T = 1 icosahedral capsid symmetry, and package a 4.7 kb single-stranded (ss) DNA genome. There are more than 100 AAV genome isolates and 13 human and non-human serotypes. The transduction efficiency of these viruses in different tissues is determined by the capsid sequence. To date, no disease has been associated with infection with wild-type AAV. In addition, AAV can transduce both dividing and non-dividing cells and maintain long-term gene expression in non-dividing cells. All these properties make them ideal vectors for therapeutic gene delivery. Recombinant AAV (rAAV) vectors used in clinical trials contain the desired transgene cassette flanked by two inverted terminal repeats (ITRs) instead of the wild-type viral genome flanked by these elements. In recent years, the AAV gene delivery system has been successfully used in multiple animal and human clinical trials. In an ongoing trial for hemophilia B, therapeutic levels of factor IX protein were maintained in patients after just one infusion of an rAAV8 vector packaging the gene for more than 2 years. In addition, an rAAV2 vector encoding a 65 kDa protein specific to the retinal pigment epithelium improved vision in patients with Leber congenital amaurosis (LCA) without any significant side effects. rAAV vectors are also being developed to transduce a variety of other cells besides the liver and eye, such as brain cells for the treatment of Parkinson's disease and Canavan disease; skeletal muscle for the treatment of emphysema, lipoprotein lipase deficiency, and muscular dystrophy; and cardiac muscle for the treatment of heart failure.