The use of prime editing—a gene-editing technique that induces small genetic changes without the need for donor DNA and without causing double strand breaks—to correct pathogenic mutations and phenotypes needs to be tested in animal models of human genetic diseases. Here we report the use of prime editors 2 and 3, delivered by hydrodynamic injection, in mice with the genetic liver disease hereditary tyrosinemia, and of prime editor 2, delivered by an adeno-associated virus vector, in mice with the genetic eye disease Leber congenital amaurosis. For each pathogenic mutation, we identified an optimal prime-editing guide RNA by using cells transduced with lentiviral libraries of guide-RNA-encoding sequences paired with the corresponding target sequences. The prime editors precisely corrected the disease-causing mutations and led to the amelioration of the disease phenotypes in the mice, without detectable off-target edits. Prime editing should be tested further in more animal models of genetic diseases.
|Number of pages||14|
|Journal||Nature biomedical engineering|
|Publication status||Published - 2022 Feb|
Bibliographical noteFunding Information:
We thank S. Kwon and J. Park for helping with computational analyses; S. Park and Y. Kim for assisting with the experiments. This work was supported by the New Faculty Startup Fund from Seoul National University (D.H.J.); the Bio and Medical Technology Development Program of the National Research Foundation funded by the Korean government, Ministry of Science, ICT and Future Planning (NRF-2017M3A9B4062401 (H.H.K. and J.H.K.)); Brain Korea 21 Four Project for Medical Sciences (Yonsei University College of Medicine); the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (NRF-2017R1A6A3A04004741 (D.H.J.)); the Medical Research Center from the National Research Foundation of Korea (2018R1A5A2025079 (H.H.K.)); grants from the National Research Foundation of Korea (2017R1A2B3004198 (H.H.K.) and 2020R1C1C1003284 (H.H.K.)); the Creative Materials Discovery Program through the National Research Foundation of Korea (NRF-2018M3D1A1058826 (J.H.K.)); the Korea Research Institute of Bioscience and Biotechnology(KRIBB) Research Initiative Program (KGM5362111 (J.H.K)); and the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (grant HI17C0676 (H.H.K.)).
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Biomedical Engineering
- Computer Science Applications