pRSET.GCaMP5G(7.35) AAV (Serotype 9)

Adeno-associated virus (AAV) is a non-pathogenic parvovirus that requires a helper virus for efficient replication and has been used as a viral vector for gene therapy due to its safety and simplicity. To date, 13 different AAV serotypes and more than 100 variants have been isolated and used as gene delivery vectors. Several AAV serotypes have been used in clinical trials. As the first capsid to be identified, AAV2 is the most widely studied and effective delivery vector for different therapeutic transgenes, such as RPE 65 for Leber congenital amaurosis, Factor IX (FIX) for hemophilia B, nerve growth factor for Alzheimer's disease, and glutamate decarboxylase for Parkinson's disease. AAV5 and 8 have also been used in multiple clinical trials for hemophilia B patients. AAV4, 9, and rh10 have been used in the eye and brain, and AAV1 and its derivative mutant AAV2.5 have been used for muscle transduction in patients with alpha-1 antitrypsin deficiency and muscular dystrophy.

For central nervous system (CNS) diseases, intraparenchymal injection is commonly used for AAV vector administration in preclinical and clinical studies. This delivery of AAV vectors directly into the brain parenchyma bypasses the blood-brain barrier (BBB), but vector diffusivity is poor, limiting transgene expression to the injection site. To achieve effective CNS and systemic muscle transduction after systemic administration, AAV vectors should be able to cross the vascular barrier. Among serotypes, AAV8 and 9 have been reported to effectively cross the endothelial barrier and transduce various tissues. AAV9, in particular, has attracted much attention for its global transduction after systemic administration. AAV9 vectors are able to cross the capillary endothelial cell barrier or BBB by transcytosis. Transcytosis is an activity that is widespread in many endothelial and epithelial cells. Currently, AAV4, 5, and 8 have also been found to be able to cross the endothelium via transcytosis.