CAG-FLEX-NES-jRGECO1b AAV (Serotype 8)

AAV8 has a wide range of tissue tropism, including brain, liver, heart, retina, lung, and muscle cells. Serotypes such as AAV2, AAV5, AAV8, and AAV9 are more commonly used to transfect hepatocytes, and studies have shown that both AAV8 and AAV9 have a strong affinity for hepatocytes, with AAV8 having the strongest hepatotropism. In mice, dogs, or primates, rAAV8 can efficiently and stably transfect hepatocytes by peripheral vein, portal vein, or intraperitoneal injection. It has been demonstrated that in the liver, AAV8-mediated target gene expression is nearly 10 to 100 times higher than other serotypes. Nakai et al. found that all hepatocytes were able to convert the incoming single-stranded vector genome into double-stranded DNA. This allows the rAAV8 vector to be stably transduced, with a transfection rate of nearly 100% at a dose of up to 7.2 × 1012 (vg/mouse) injected via the portal vein. Transfection did not result in any hepatotoxicity, and the procedure was able to deliver 2.5 times more DNA to the liver compared to intramuscular injection. AAV8 vectors can also transfect cells in other tissues, including muscle, heart, pancreas, and brain. In neonatal dogs, a single jugular vein injection of AAV8 presented extensive and durable systemic transduction in skeletal and cardiac muscle, and this expression persisted in the heart for at least one year. In addition, rAAV8 can efficiently transduce the brain. Stereotactic brain injections were performed to compare the transfection efficiency of different serotypes in different brain regions. Transgene expression of rAAV8 in glial cells was significant. In addition, intramuscular injection of rAAV8 resulted in efficient and stable transduction of spinal cord white matter, dorsal root ganglion neurons, and peripheral nerves in neonatal mice, with more neurons in the lower spinal cord transduced than in the upper spinal cord.