543. Efficient Neuronal But Limited Glia Transduction by AAVshH10 in Dorsal Root Ganglion and Spinal Cord of Adult Rats

Abstract

Recombinant adeno-associated viral (AAV)-mediated therapeutic gene transfer is an effective and safe tool for the treatment of chronic pain. Activated glial cells play important roles in pain pathophysiology and are promising targets for the therapeutic intervention. However, the natural tropism of AAV vectors leads to gene transfer predominantly to neurons while glial cells are refractory to AAV transduction in both the central and peripheral nervous system (CNS and PNS). AAVshH10 is a recently engineered novel AAV6-like variant that demonstrates efficient and selective Muller glia transduction in the retina. The present study was designed to evaluate whether in vivo glia transduction in the dorsal root ganglion (DRG) and the spinal cord (SC) could be enhanced using AAVshH10. Titer-matched AAVshH10 and original AAV6, both encoding the enhanced green fluorescent protein (EGFP) reporter driven by the ubiquitous cell-potent CMV promoter, were injected into DRGs and spinal cords (SCs) of adult rats. Neurotropism of gene transfer by AAVshH10 in comparison to AAV6 was determined by immunohistochemistry. Results showed that injection of AAVshH10 into DRGs and SCs resulted in a similar profile to its parent AAV6, both showing efficient transduction of all sub-populations of sensory neurons in DRGs or the neurons in SCs, without significant transduction of glial cell populations in both sites. Together, this study demonstrates an efficient neuronal but limited glia transduction of AAVshH10, which can be used as a viable alternative to AAV6 for efficient neuronal transduction in DRGs and SCs.