In vivo base editing restores sensory transduction and transiently improves auditory function in a mouse model of recessive deafness.
Wei-Hsi Yeh, Olga Shubina-Oleinik, Jonathan M Levy, Bifeng Pan, Gregory A Newby, Michael Wornow, Rachel Burt, Jonathan C Chen, Jeffrey R Holt, David R Liu
Sci Transl Med | Published : 2020
Most genetic diseases arise from recessive point mutations that require correction, rather than disruption, of the pathogenic allele to benefit patients. Base editing has the potential to directly repair point mutations and provide therapeutic restoration of gene function. Mutations of transmembrane channel-like 1 gene (TMC1) can cause dominant or recessive deafness. We developed a base editing strategy to treat Baringo mice, which carry a recessive, loss-of-function point mutation (c.A545G; resulting in the substitution p.Y182C) in Tmc1 that causes deafness. Tmc1 encodes a protein that forms mechanosensitive ion channels in sensory hair cells of the inner ear and is required for normal audi..View full abstract