CAG-FLEX-GCaMP6s AAV (Serotype 8)

Adeno-associated virus (AAV) is an increasingly popular gene transfer vector that offers many inherent advantages over other vectors, including nonpathogenicity and the ability to mediate long-term gene expression in a variety of tissues in vivo. A particular benefit is the ability to combine recombinant AAV genomes (usually from the AAV serotype 2 [AAV2] prototype) with capsids from more than 100 identified natural human or non-human virus isolates or engineer them by capsid DNA shuffling or mutagenesis Synthetic "design" shells are faked. This results in vector particles with unique properties, including unique tissue biodistribution and transduction properties, thereby significantly increasing the versatility of AAV vector systems. To date, AAV2 has been the predominant serotype tested in clinical trials, but a number of alternative serotypes with specific advantages for certain diseases are currently in preclinical development. Of these, perhaps the most interesting candidate is AAV8. In fact, despite an 83% amino acid similarity between the two viruses, AAV8 transduces 20-fold more efficiently than AAV2 in mouse livers. The higher rate of capsid uncoating of AAV8 compared to AAV2 may account for the increased transduction efficiency, allowing AAV8 to transduce nearly 100% of hepatocytes. A second advantage of AAV8 is that, since it is a primate virus (isolated from rhesus monkeys), vectors derived from it are likely not to be recognized by existing antibodies in humans and therefore less likely to cause Adverse immune side effects. In contrast, the use of AAV2 vectors in humans is limited due to the prevalence of humoral immunity in the population and the risk of inducing cellular immune responses in vivo against capsid-containing cells.