Abraham Sheffield - DFNA3; gene therapy

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I am working on genetic therapeutics for GJB2-related hearing loss. Mutations in GJB2 are the most common cause of genetic deafness, accounting for 30-60% of autosomal recessive non-syndromic hearing loss in Europe and the United States. Mutations in GJB2 are also known to cause autosomal dominant forms of deafness, including syndromic hearing loss segregating with skin disease. GJB2 encodes connexin26 (Cx26), a gap junction protein expressed in the supporting cells of the organ of Corti. My goal is to use gene therapy to improve the hearing loss phenotype in a transgenic mouse model of a dominant-negative GJB2 mutation. My research includes:

• Optimization of viral vector delivery to cochlear supporting cells via transuterine microinjection of the embryonic mouse otocyst.

• Design and optimization of RNAi targeting dominant-negative GJB2 mutations.

• Delivery of therapeutic RNAi to the developing cochlea of genetically deaf mice.