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bioRxiv · 10.1101/2022.06.20.496770

In vivo base editing rescues photoreceptors in a mouse model of retinitis pigmentosa

Yang, Y.·Su, J.·She, K.·Song, L.·Jin, X.·Li, R.·Zhao, Q.·Xiao, J.·Chen, D.·Cheng, H.·Lu, F.·Wei, Y.
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Abstract

Retinitis pigmentosa (RP) is a group of retinal diseases that cause the progressive death of retinal photoreceptor cells and eventually blindness. Mutations in the {beta}-domain of the phosphodiesterase 6 (Pde6b) gene are among the most identified causes of autosomal recessive RP. Here, we report a base editing approach in which adeno-associated virus (AAV)-mediated adenine base editor (ABE) delivery to postmitotic photoreceptors is used to correct the Pde6b mutation in a retinal degeneration 10 (rd10) mouse model of RP. Subretinal delivery of AAV8-ABE corrects Pde6b mutation with up to 37.41% efficiency at the DNA level and up to 91.95% efficiency at the cDNA level, restores PDE6B expression, preserves photoreceptors and rescues visual function. RNA-seq reveals upregulation of genes associated with phototransduction and photoreceptor survival. Our data demonstrate that base editing is a potential gene therapy that could provide durable protection against RP.

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Yang, Y., Su, J., She, K., Song, L., Jin, X., Li, R., Zhao, Q., Xiao, J., Chen, D., Cheng, H., Lu, F., Wei, Y.. 2022-06-22. In vivo base editing rescues photoreceptors in a mouse model of retinitis pigmentosa. https://doi.org/10.1101/2022.06.20.496770

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