AAV8-CAG-NLuc-2A-mCherry

Recombinant adeno-associated virus (AAV) vectors have attracted much attention as gene therapy vectors due to their lack of pathogenicity and ability to infect different tissues. To date, 12 serotypes of AAV (AAV1 to AAV12) vectors have been extensively studied as gene therapy vectors. These AAV serotypes share a common genome, but their unique capsid structures help them recognize different cell surface receptors. AAV serotype 2 is the most extensively studied, but has limited preclinical success. Capsid antigens of AAV2 are known to elicit cytotoxic T cell responses, as demonstrated in liver-directed gene therapy for patients with hemophilia B. To overcome this limitation imposed by AAV2 vectors, alternative AAV serotypes are being rigorously evaluated for liver gene transfer. AAV serotype 8, in particular, has consistently demonstrated significant transduction efficiency (10- to 100-fold) and reduced immunogenicity compared to AAV2 vectors. Importantly, peripheral intravenous administration of AAV8 vectors has been highly effective in the context of liver gene transfer, indicating that these vectors have a high liver targeting ability. Furthermore, the long-term safety and efficacy of AAV8 vectors during liver gene therapy have been demonstrated not only in mice but also in canine and primate models. In addition, rAAV8 can effectively transduce the brain. Stereotactic brain injections were performed to compare the transfection efficiency of different serotypes in different brain regions. rAAV8 showed significant transgene expression in glial cells. In addition, after intramuscular injection of rAAV8, efficient and stable transduction was found in the white matter, dorsal root ganglion neurons, and peripheral nerves of the spinal cord of newborn mice. Specifically, more neurons were transduced in the lower part of the spinal cord than in the upper part.