CAG-iCre-T2A-GFP AAV (Serotype BR1)

In neural circuit analysis and gene therapy, many research scenarios require gene delivery to the whole brain. Common neurological diseases include lysosomal storage diseases, Alzheimer's disease, Parkinson's disease, etc., which have extensive pathological manifestations and affect multiple areas of the brain. AAV has attracted widespread attention due to its wide host range, low immunogenicity, and ability to maintain high levels of transgenic expression for a long time. It is considered to be a therapeutic vector with great clinical application prospects. However, the existence of the blood-brain barrier significantly hinders most molecules such as AAV from entering the brain, limiting their application in brain research and brain disease treatment. Therefore, there is an urgent need to develop AAV vectors that can efficiently and specifically cross the blood-brain barrier to provide new and powerful tools for neural circuit analysis and brain disease treatment.

At present, the choice of AAV application is mainly concentrated in two aspects. The first is to explore the application of natural serotype AAV, such as AAV9, AAVrh.8, AAVrh.10, etc., which can cross the BBB into the brain parenchyma after systemic administration and effectively transduce cells in the central nervous system; AAV1 can mediate anterograde transsynaptic labeling, while AAV11 can effectively reversely target projection neurons and enhance directional transduction to astrocytes. The second is to modify the existing AAV capsid protein to give it new functional properties, thereby making up for the functional defects of natural serotype AAV. At present, the methods for modifying viral capsid proteins mainly include directed evolution, rational design, computer-aided design and chemical binding technology. A large number of excellent mutants have been developed based on the directed evolution method, among which the AAV-BR1 mutant can effectively transduce brain vascular endothelial cells.