AAV8-CMV-FLPo

Adeno-associated viral vector serotype 8 (AAV8) has been widely used to transduce hepatocytes, the major parenchymal cells in the liver. AAV8 is considered an ideal approach to target hepatocytes due to its liver tropism, low immunogenicity, low toxicity, and high transduction efficiency of hepatocytes. Neonatal injection of AAV is associated with attenuated neutralizing antibody responses and has been proposed as a promising strategy to correct early-onset congenital diseases.

Previous studies have shown that the transduction efficiency and tropism of AAV vectors depend on several variables. These variables include capsid serotype, promoter, vector dose, route of injection, and timing of injection, suggesting that characterizing the neonatal liver response to AAV is important. It is becoming increasingly clear that non-hepatocytes in the liver, such as cholangiocytes, endothelial cells, and fibroblasts, contribute to normal liver function as well as disease progression, meaning that nonspecific infection of non-parenchymal cells could lead to side effects. Conversely, if AAV8 transduces non-parenchymal cells, this could lead to a wider application of AAV8 vectors. Therefore, an accurate understanding of the cell tropism of AAV8 could improve study design and gene therapy.