No observable guide-RNA-independent off-target mutation induced by prime editor

Gao, R.; Fu, Z.-C.; Li, X.; Wang, Y.; Wei, J.; Li, G.; Wang, L.; Wu, J.; Xue, W.; Huang, X.; Yang, L.; Chen, J.

doi:10.1101/2021.04.09.439109

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bioRxiv · 10.1101/2021.04.09.439109

No observable guide-RNA-independent off-target mutation induced by prime editor

Gao, R.·Fu, Z.-C.·Li, X.·Wang, Y.·Wei, J.·Li, G.·Wang, L.·Wu, J.·Xue, W.·Huang, X.·Yang, L.·Chen, J.

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Abstract

Prime editor (PE) has been recently developed to induce efficient and precise ontarget editing, whereas its guide RNA (gRNA)-independent off-target effects remain unknown. Here, we used whole-genome and whole-transcriptome sequencing to determine gRNA-independent off-target mutations in cells expanded from single colonies, in which PE generated precise editing at on-target sites. We found that PE triggered no observable gRNA-independent off-target mutation genome-wide or transcriptome-wide in transfected human cells, highlighting its high specificity.

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Gao, R., Fu, Z.-C., Li, X., Wang, Y., Wei, J., Li, G., Wang, L., Wu, J., Xue, W., Huang, X., Yang, L., Chen, J.. 2021-04-09. No observable guide-RNA-independent off-target mutation induced by prime editor. https://doi.org/10.1101/2021.04.09.439109

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