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bioRxiv · 10.1101/2021.01.08.425835

Prime editing enables precise genome editing in mouse liver and retina

Jang, H.·Shin, J. H.·Jo, D. H.·Seo, J. H.·Yu, G.·Gopalappa, R.·Cho, S.-R.·Kim, J. H.·Kim, H. H.
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Abstract

Prime editing can induce any small-sized genetic change without donor DNA or double strand breaks. However, it has not been investigated whether prime editing is possible in postnatal animals. Here we delivered prime editors 2 and 3 into a mouse model of hereditary tyrosinemia, a genetic liver disease, using hydrodynamic injection, which corrected the disease-causing mutation and rescued the phenotype. We also achieved prime editing in the retina and retina pigment epithelium in wild-type mice by delivering prime editor 3 using trans-splicing adeno-associated virus. Deep sequencing showed that unintended edits at or near the target site or off-target effects were not detectable except for low levels (0% to 1.2%) of indels when PE3, but not PE2, was used. Our study suggests that precise, prime editor-mediated genome editing is possible in somatic cells of adult animals.

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Jang, H., Shin, J. H., Jo, D. H., Seo, J. H., Yu, G., Gopalappa, R., Cho, S.-R., Kim, J. H., Kim, H. H.. 2021-01-08. Prime editing enables precise genome editing in mouse liver and retina. https://doi.org/10.1101/2021.01.08.425835

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