AAV7m8-CAG-GFP

Adeno-associated virus (AAV) is a small single-stranded (ss) DNA virus that belongs to the Parvoviridae family. Recombinant (r) AAV vectors have all viral genes removed and are considered non-pathogenic. In addition, rAAV has low immunological properties compared to other viral vectors. These properties make it the most widely used vector in gene therapy, especially for the treatment of ocular diseases. rAAV has demonstrated its efficacy in clinical trials for inherited retinal dystrophies, including Leber congenital amaurosis (LCA), choroideremia, and X-linked retinitis pigmentosa. Currently, there is an FDA-approved gene therapy (Luxterna) for the treatment of LCA. Despite the success of rAAV in gene therapy in recent years, such as in the liver, central nervous system, and skeletal muscle, there are still some obstacles that hinder the wider application of ocular gene therapy. AAV2.7m8 is an engineered capsid with 10 amino acids inserted into each of the triple spikes of AAV2 and was discovered through a “7-mer” library screen designed to identify capsids capable of transducing mouse photoreceptor cells. Notably, the first three amino acids act as a linker to ensure the structural integrity of the 7-mer insert. The defining residues of 7m8 (LALGETTRPA) are inserted into the AAV2 VP1 capsid sequence at amino acid position 588, which is located in the outermost protruding region of the capsid surface. The insertion also disrupts the basic arginine residues in hypervariable region VIII that are involved in the binding of AAV2 to its primary receptor, heparan sulfate proteoglycans (HSPGs). AAV2.7m8 also demonstrated strong transduction of mouse inner ear tissue, suggesting that it may be a promising vector for delivering therapeutic genes to prevent or reverse inherited hearing loss.