Prime editor-mediated correction of a pathogenic mutation in purebred dogs

Prime 编辑器介导的纯种犬致病突变校正

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作者:Dong Ern Kim, Ji Hye Lee, Kuk Bin Ji, Eun Ji Lee, Chuang Li, Hyun Ju Oh, Kang Sun Park, Seung Hoon Lee, Okjae Koo, Min Kyu Kim

Abstract

Canine hip dysplasia (HD) is a multifactorial disease caused by interactions between genetic and environmental factors. HD, which mainly occurs in medium- to large-sized dogs, is a disease that causes severe pain and requires surgical intervention. However, the procedure is not straight-forward, and the only way to ameliorate the situation is to exclude individual dogs with HD from breeding programs. Recently, prime editing (PE), a novel genome editing tool based on the CRISPR-Cas9 system, has been developed and validated in plants and mice. In this study, we successfully corrected a mutation related to HD in Labrador retriever dogs for the first time. We collected cells from a dog diagnosed with HD, corrected the mutation using PE, and generated mutation-corrected dogs by somatic cell nuclear transfer. The results indicate that PE technology can potentially be used as a platform to correct genetic defects in dogs.

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