AAV-Null (Serotype BR1)

The blood-brain barrier (BBB), which limits the passage of harmful molecules from the blood circulation, remains a major obstacle to drug delivery to the brain, necessitating improved drug delivery strategies. The BBB is composed of brain endothelial cells (BECs) that line the capillary walls and are supported by pericyte and astrocyte endfeet. It controls the entry of molecules into the brain to maintain a stable microenvironment, which is essential for normal neuronal function. Several different approaches have been explored to overcome the BBB, such as using hyperosmotic solutes and focused ultrasound to temporarily increase the permeability of the BBB, directly infusing compounds into the brain, and exploiting existing BBB nutrient transport mechanisms. However, these efforts are often associated with a risk of serious adverse events, limited distribution within the brain, or low brain specificity.

Other strategies used to enhance BBB crossing include the design of adeno-associated viral (AAV) vectors. The BEC-targeting AAV capsid mutant, “AAV-BR1,” was previously selected in mice after multiple rounds of screening against a random AAV2-displayed peptide library. AAV-BR1 was isolated from the AAV2 library and contains the amino acid sequence "NRGTEWD" in its capsid. AAV-BR1 is an important tool for researchers focusing on brain endothelial cell function.