scAAV ShH10-CAG-GFP

Wild-type AAV is a small virus of the Parvoviridae family, 4.7 kb in size, and is a linear single-stranded DNA (ssDNA). They are composed of an icosahedral protein capsid containing three subunits (VP1, VP2, and VP3) in a total of 60 copies in a 1:1:10 ratio (VP1:VP2:VP3). Its genome contains a rep gene encoding four proteins required for viral replication; a cap gene encoding three capsid subunits through alternative splicing and translation from different start codons; and a gene encoding assembly activation protein (AAP), which promotes virion assembly. These genes are flanked by inverted terminal repeats (ITRs), which are required to direct genome replication and packaging. For therapeutic use, the rep and cap genes are removed and replaced with an expression cassette containing a therapeutic transgene under the control of a promoter and flanked by AAV ITR sequences, resulting in recombinant adeno-associated virus (rAAV). There are hundreds of variants of AAV, including 11 natural serotypes: AAV 1-11.

Recombinant adeno-associated virus (AAV)-mediated therapeutic gene transfer is an effective and safe tool for the treatment of chronic pain. Activated glial cells play an important role in pain pathophysiology and are promising targets for therapeutic intervention. However, the natural tropism of AAV vectors results in gene transfer mainly to neurons, while glial cells in the central nervous system (CNS) and peripheral nervous system (PNS) are resistant to AAV transduction. AAVshH10 is a recently designed novel variant similar to AAV6 that can efficiently and selectively transduce Muller glial cells in the retina. Titer-matched AAVshH10 and original AAV6 were injected into dorsal root ganglia (DRG) and spinal cord (SC) of adult rats. The results showed that injection of AAVshH10 into DRG and SC showed similar results to its parental AAV6, with both being able to effectively transduce all sensory neuron subsets in DRG or neurons in SC, and no significant transduction of glial cell populations in both sites.