Hongwei Yu, MD

Gene and molecular therapy for chronic pain

Our research focuses are on designing, cloning, production, and application of recombinant adeno-associated viral (AAV) vectors to manipulate genes of interests in vivo in the peripheral sensory nervous system for studying pain molecular mechanism and for treating chronic pain. Directed by Dr. Quinn Hogan, we have successfully developed AAV vectors for mechanistic research and translational development. These AAV vectors have high transduction efficiency for all sensory neuron subtypes or have selective tropism to large-sized Aβ low-threshold mechanoreceptors when delivered into dorsal root ganglia (DRG) in rodent. We have recently defined a novel strategy, AAV-encoded interfering peptide aptamers (AAV-iPAs), for reversing pain by modulating the pain interactome in the peripheral nervous system. We have demonstrated the efficacy of AAV-iPAs approach using iPA targeting various TRP and voltage-gated calcium channels. We are also developing other AAV systems (AAV-targeted Optogenetics, AAV-siRNA in vivo gene knockdown, and vectors that can reconstitute transgene across synaptic partners in the first sensory synapses).

Satellite glial cells (SGCs) wrapping the primary sensory neurons together compose of unique anatomical and functional sensory units in the DRG. We recently develop a SGC-specific AAV vector (sgcAAV) that is effective in providing SGC-selective transgene expression following intraganglionic sgcAAV delivery in adult rats, and we also developed a microglia-specific AAV vector (mgAAV) by using the promoter of Iba1 gene that is a canonical microglial marker. These glial cell-targeting AAV strategies should prove useful for the development of gene expression systems targeting SGC and microglial signaling for chronic pain. We have also established a dual AAV strategy using two AAV vectors enabling efficient expression of transgenes selectively in neurons versus SGCs.