AAV9-CBh-GFP-2A-FLuc

Gene therapy based on engineered viruses has become a very promising general approach for treating human diseases. In particular, recombinant vectors or vectors based on adeno-associated viruses (AAV) have emerged as safe and effective gene therapy vectors. Their advantages include strong clinical safety, the ability to promote high transgene expression in both dividing and non-dividing cells, minimal integration risk, and low immunogenicity. AAV has been applied to gene delivery in several organs, such as the liver for hemophilia B, the muscle for spinal muscular atrophy, and the eyes for inherited retinal dystrophy or Leber congenital amaurosis, and has been entered into clinical trials recently. AAV vectors have proven to be a very useful tool, primarily for delivering genes to the central nervous system for the treatment of neurological diseases. In particular, AAV9 is the most commonly used serotype, with a clear tropism for the central nervous system, especially for motor neurons when combined with the CBh or CBA promoters. AAV9 carrying the giant axonal protein gene has been used to treat giant axonal neuropathy (GAN) and has also provided expression of the SMN1 gene, which is currently used for the treatment of spinal muscular atrophy (SMA) via intravenous or intrathecal delivery. In addition, subpial delivery of AAV9 carrying shRNA to the spinal cord prevents spinal cord atrophy in the familial amyotrophic lateral sclerosis (FALS) SOD1(G93A) mouse model.