Doudna, J. A. The promise and challenge of therapeutic genome editing. Nature 578, 229–236 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Anzalone, A. V., Koblan, L. W. & Liu, D. R. Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors. Nat. Biotechnol. 38, 824–844 (2020).

Article  CAS  PubMed  Google Scholar 

van Overbeek, M. et al. DNA repair profiling reveals nonrandom outcomes at Cas9-mediated breaks. Mol. Cell 63, 633–646 (2016).

Article  PubMed  Google Scholar 

Shen, M. W. et al. Predictable and precise template-free CRISPR editing of pathogenic variants. Nature 563, 646–651 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kosicki, M., Tomberg, K. & Bradley, A. Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements. Nat. Biotechnol. 36, 765–771 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Leibowitz, M. L. et al. Chromothripsis as an on-target consequence of CRISPR–Cas9 genome editing. Nat. Genet. 53, 895–905 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kosicki, M. et al. Cas9-induced large deletions and small indels are controlled in a convergent fashion. Nat. Commun. 13, 3422 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Alanis-Lobato, G. et al. Frequent loss of heterozygosity in CRISPR–Cas9-edited early human embryos. Proc. Natl Acad. Sci. USA 118, e2004832117 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Enache, O. M. et al. Cas9 activates the p53 pathway and selects for p53-inactivating mutations. Nat. Genet. 52, 662–668 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Haapaniemi, E., Botla, S., Persson, J., Schmierer, B. & Taipale, J. CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response. Nat. Med. 24, 927–930 (2018).

Article  CAS  PubMed  Google Scholar 

Ihry, R. J. et al. p53 inhibits CRISPR–Cas9 engineering in human pluripotent stem cells. Nat. Med. 24, 939–946 (2018).

Article  CAS  PubMed  Google Scholar 

Cullot, G. et al. CRISPR–Cas9 genome editing induces megabase-scale chromosomal truncations. Nat. Commun. 10, 1136 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Cullot, G. et al. Cell cycle arrest and p53 prevent ON-target megabase-scale rearrangements induced by CRISPR–Cas9. Nat. Commun. 14, 4072 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Boutin, J. et al. CRISPR–Cas9 globin editing can induce megabase-scale copy-neutral losses of heterozygosity in hematopoietic cells. Nat. Commun. 12, 4922 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tsai, H.-H. et al. Whole genomic analysis reveals atypical non-homologous off-target large structural variants induced by CRISPR–Cas9-mediated genome editing. Nat. Commun. 14, 5183 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hustedt, N. & Durocher, D. The control of DNA repair by the cell cycle. Nat. Cell Biol. 19, 1–9 (2017).

Article  CAS  Google Scholar 

Yeh, C. D., Richardson, C. D. & Corn, J. E. Advances in genome editing through control of DNA repair pathways. Nat. Cell Biol. 21, 1468–1478 (2019).

Article  CAS  PubMed  Google Scholar 

Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A. & Liu, D. R. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533, 420–424 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gaudelli, N. M. et al. Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature 551, 464–471 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rees, H. A. & Liu, D. R. Base editing: precision chemistry on the genome and transcriptome of living cells. Nat. Rev. Genet. 19, 770–788 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Grünewald, J. et al. Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors. Nature 569, 433–437 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Zuo, E. et al. Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos. Science 364, 289–292 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Park, S. & Beal, P. A. Off-target editing by CRISPR-guided DNA base editors. Biochemistry 58, 3727–3734 (2019).

Article  CAS  PubMed  Google Scholar 

Huang, T. P., Newby, G. A. & Liu, D. R. Precision genome editing using cytosine and adenine base editors in mammalian cells. Nat. Protoc. 16, 1089–1128 (2021).

Article  CAS  PubMed  Google Scholar 

Porto, E. M., Komor, A. C., Slaymaker, I. M. & Yeo, G. W. Base editing: advances and therapeutic opportunities. Nat. Rev. Drug Discovery 19, 839–859 (2020).

Article  CAS  PubMed  Google Scholar 

Halperin, S. O. et al. CRISPR-guided DNA polymerases enable diversification of all nucleotides in a tunable window. Nature 560, 248–252 (2018).

Article  CAS  PubMed  Google Scholar 

Tou, C. J., Schaffer, D. V. & Dueber, J. E. Targeted diversification in the S. cerevisiae genome with CRISPR-guided DNA polymerase I. ACS Synth. Biol. 9, 1911–1916 (2020).

Article  CAS  PubMed  Google Scholar 

Long, M. et al. Directed evolution of ornithine cyclodeaminase using an EvolvR-based growth-coupling strategy for efficient biosynthesis of l-proline. ACS Synth. Biol. 9, 1855–1863 (2020).

Article  CAS  PubMed  Google Scholar 

Gossing, M. et al. Multiplexed guide RNA expression leads to increased mutation frequency in targeted window using a CRISPR-guided error-prone DNA polymerase in Saccharomyces cerevisiae. ACS Synth. Biol. 12, 2271–2277 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nakade, S. et al. Frame editors for precise, template-free frameshifting. Preprint at https://doi.org/10.1101/2022.12.05.518807 (2022).

Yang, Q. et al. Phage DNA polymerase prevents on-target damage and enhances precision of CRISPR editing. Preprint at https://doi.org/10.1101/2023.01.10.523496 (2023).