Deep learning models to predict the editing efficiencies and outcomes of diverse base editors

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 

Kurt, I. C. et al. CRISPR C-to-G base editors for inducing targeted DNA transversions in human cells. Nat. Biotechnol. 39, 41–46 (2021).

Article  CAS  PubMed  Google Scholar 

Zhao, D. et al. Glycosylase base editors enable C-to-A and C-to-G base changes. Nat. Biotechnol. 39, 35–40 (2021).

Article  CAS  PubMed  Google Scholar 

Chen, L. et al. Programmable C:G to G:C genome editing with CRISPR-Cas9-directed base excision repair proteins. Nat. Commun. 12, 1384 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Koblan, L. W. et al. Efficient C*G-to-G*C base editors developed using CRISPRi screens, target-library analysis, and machine learning. Nat. Biotechnol. 39, 1414–1425 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Komor, A. C. et al. Improved base excision repair inhibition and bacteriophage Mu Gam protein yields C:G-to-T:A base editors with higher efficiency and product purity. Sci. Adv. 3, eaao4774 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Doman, J. L., Raguram, A., Newby, G. A. & Liu, D. R. Evaluation and minimization of Cas9-independent off-target DNA editing by cytosine base editors. Nat. Biotechnol. 38, 620–628 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yu, Y. et al. Cytosine base editors with minimized unguided DNA and RNA off-target events and high on-target activity. Nat. Commun. 11, 2052 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Richter, M. F. et al. Author correction: Phage-assisted evolution of an adenine base editor with improved Cas domain compatibility and activity. Nat. Biotechnol. 38, 901 (2020).

Article  CAS  PubMed  Google Scholar 

Gaudelli, N. M. et al. Directed evolution of adenine base editors with increased activity and therapeutic application. Nat. Biotechnol. 38, 892–900 (2020).

Article  CAS  PubMed  Google Scholar 

Kleinstiver, B. P. et al. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature 523, 481–485 (2015).

Article  PubMed  PubMed Central  Google Scholar 

Kleinstiver, B. P. et al. High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature 529, 490–495 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Anders, C., Bargsten, K. & Jinek, M. Structural plasticity of PAM recognition by engineered variants of the RNA-guided endonuclease Cas9. Mol. Cell 61, 895–902 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hu, J. H. et al. Evolved Cas9 variants with broad PAM compatibility and high DNA specificity. Nature 556, 57–63 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nishimasu, H. et al. Engineered CRISPR-Cas9 nuclease with expanded targeting space. Science 361, 1259–1262 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Miller, S. M. et al. Continuous evolution of SpCas9 variants compatible with non-G PAMs. Nat. Biotechnol. 38, 471–481 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Walton, R. T., Christie, K. A., Whittaker, M. N. & Kleinstiver, B. P. Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants. Science 368, 290–296 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chatterjee, P. et al. An engineered ScCas9 with broad PAM range and high specificity and activity. Nat. Biotechnol. 38, 1154–1158 (2020).

Article  CAS  PubMed  Google Scholar 

Chatterjee, P. et al. A Cas9 with PAM recognition for adenine dinucleotides. Nat. Commun. 11, 2474 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim, N. et al. Prediction of the sequence-specific cleavage activity of Cas9 variants. Nat. Biotechnol. 38, 1328–1336 (2020).

Article  CAS  PubMed  Google Scholar 

Koblan, L. W. et al. Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction. Nat. Biotechnol. 36, 843–846 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zafra, M. P. et al. Optimized base editors enable efficient editing in cells, organoids and mice. Nat. Biotechnol. 36, 888–893 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cong, L. et al. Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819–823 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim, H. K. et al. SpCas9 activity prediction by DeepSpCas9, a deep learning-based model with high generalization performance. Sci. Adv. 5, eaax9249 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Song, M. et al. Sequence-specific prediction of the efficiencies of adenine and cytosine base editors. Nat. Biotechnol. 38, 1037–1043 (2020).

Article  CAS  PubMed  Google Scholar 

Kim, H. K. et al. High-throughput analysis of the activities of xCas9, SpCas9-NG and SpCas9 at matched and mismatched target sequences in human cells. Nat. Biomed. Eng. 4, 111–124 (2020).

Article  CAS  PubMed  Google Scholar 

Hill, A. J. et al. On the design of CRISPR-based single-cell molecular screens. Nat. Methods 15, 271–274 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim, H. K. et al. Predicting the efficiency of prime editing guide RNAs in human cells. Nat. Biotechnol. 39, 198–206 (2021).

Article  CAS  PubMed  Google Scholar 

Jin, S. et al. Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice. Science 364, 292–295 (2019).

Article  CAS  PubMed  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 

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

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim, Y. B. et al. Increasing the genome-targeting scope and precision of base editing with engineered Cas9-cytidine deaminase fusions. Nat. Biotechnol. 35, 371–376 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Arbab, M. et al. Determinants of base editing outcomes from target library analysis and machine learning. Cell 182, 463–480 e430 (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).

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