forward. Cell 172: 1239–1259.77 Hirano, H., Gootenberg, J.S., Horii, T. et al. (2016). Structure and engineering of Francisella novicida Cas9. Cell 164: 950–961.
78 Horvath, P., Romero, D.A., Coute‐Monvoisin, A.C. et al. (2008). Diversity, activity, and evolution of CRISPR loci in Streptococcus thermophilus. J. Bacteriol. 190: 1401–1412.
79 Hou, Z., Zhang, Y., Propson, N.E. et al. (2013). Efficient genome engineering in human pluripotent stem cells using Cas9 from Neisseria meningitidis. Proc. Natl. Acad. Sci. U. S. A. 110: 15644–15649.
80 Hu, Z., Wang, S., Zhang, C. et al. (2020). A compact Cas9 ortholog from Staphylococcus Auricularis (SauriCas9) expands the DNA targeting scope. PLoS Biol. 18: e3000686.
81 Huo, Y., Nam, K.H., Ding, F. et al. (2014). Structures of CRISPR Cas3 offer mechanistic insights into Cascade‐activated DNA unwinding and degradation. Nat. Struct. Mol. Biol. 21: 771–777.
82 Hwang, W.Y., Fu, Y., Reyon, D. et al. (2013). Efficient genome editing in zebrafish using a CRISPR‐Cas system. Nat. Biotechnol. 31: 227–229.
83 Hynes, A.P., Villion, M., and Moineau, S. (2014). Adaptation in bacterial CRISPR‐Cas immunity can be driven by defective phages. Nat. Commun. 5: 1–6.
84 Ishino, Y., Shinagawa, H., Makino, K. et al. (1987). Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J. Bacteriol. 169: 5429–5433.
85 Ivančić‐Baće, I., Cass, S.D., Wearne, S.J., and Bolt, E.L. (2015). Different genome stability proteins underpin primed and naïve adaptation in E. coli CRISPR‐Cas immunity. Nucleic Acids Res. 43: 10821–10830.
86 Jansen, R., Van Embden, J.D.A., Gaastra, W., and Schouls, L.M. (2002). Identification of genes that are associated with DNA repeats in prokaryotes. Mol. Microbiol. 43: 1565–1575.
87 Jeon, Y., Choi, Y.H., Jang, Y. et al. (2018). Direct observation of DNA target searching and cleavage by CRISPR‐Cas12a. Nat. Commun. 9: 2777.
88 Jiang, F., Taylor, D.W., Chen, J.S. et al. (2016a). Structures of a CRISPR‐Cas9 R‐loop complex primed for DNA cleavage. Science 351: 867–871.
89 Jiang, W., Samai, P., and Marraffini, L.A. (2016b). Degradation of phage transcripts by CRISPR‐associated RNases enables Type III CRISPR‐Cas Immunity. Cell 164: 710–721.
90 Jinek, M., Chylinski, K., Fonfara, I. et al. (2012). A programmable dual‐RNA‐guided DNA endonuclease in adaptive bacterial immunity. Science 337: 816–821.
91 Jinek, M., East, A., Cheng, A. et al. (2013). RNA‐programmed genome editing in human cells. elife 2: e00471.
92 Jore, M.M., Lundgren, M., Van Duijn, E. et al. (2011). Structural basis for CRISPR RNA‐guided DNA recognition by Cascade. Nat. Struct. Mol. Biol. 18: 529–536.
93 Jones, J.R.S.K., Hawkins, J.A., Johnson, N.V. et al. (2020). Massively parallel kinetic profiling of natural and engineered CRISPR nucleases. Nat. Biotechnol. 39: 84–93.
94 Karvelis, T., Gasiunas, G., Miksys, A. et al. (2013). crRNA and tracrRNA guide Cas9‐mediated DNA interference in streptococcus thermophilus. RNA Biol. 10: 841–851.
95 Karvelis, T., Bigelyte, G., Young, J.K. et al. (2020). PAM recognition by miniature CRISPR‐Cas12f nucleases triggers programmable double‐stranded DNA target cleavage. Nucleic Acids Res. 48: 5016–5023.
96 Kazlauskiene, M., Tamulaitis, G., Kostiuk, G. et al. (2016). Spatiotemporal control of Type III‐A CRISPR‐Cas Immunity: coupling DNA degradation with the target RNA recognition. Mol. Cell 62: 295–306.
97 Kazlauskiene, M., Kostiuk, G., Venclovas, C. et al. (2017). A cyclic oligonucleotide signaling pathway in Type III CRISPR‐Cas systems. Science 357: 605–609.
98 Kim, E., Koo, T., Park, S.W. et al. (2017). in vivo genome editing with a small Cas9 orthologue derived from Campylobacter jejuni. Nat. Commun. 8: 14500.
99 Kim, S., Loeff, L., Colombo, S. et al. (2020). Selective loading and processing of prespacers for precise CRISPR adaptation. Nature 579: 141–145.
100 Kiro, R., Shitrit, D., and Qimron, U. (2014). Efficient engineering of a bacteriophage genome using the type I‐E CRISPR‐Cas system. RNA Biol. 11: 42–44.
101 Klein, M., Eslami‐Mossallam, B., Arroyo, D.G., and Depken, M. (2018). Hybridization kinetics explains CRISPR‐Cas off‐targeting rules. Cell Rep. 22: 1413–1423.
102 Kleinstiver, B.P., Prew, M.S., Tsai, S.Q. et al. (2015). Engineered CRISPR‐Cas9 nucleases with altered PAM specificities. Nature 523: 481–485.
103 Kleinstiver, B.P., Pattanayak, V., Prew, M.S. et al. (2016a). High‐fidelity CRISPR‐Cas9 nucleases with no detectable genome‐wide off‐target effects. Nature 529: 490–495.
104 Kleinstiver, B.P., Tsai, S.Q., Prew, M.S. et al. (2016b). Genome‐wide specificities of CRISPR‐Cas Cpf1 nucleases in human cells. Nat. Biotechnol. 34: 869–874.
105 Kleinstiver, B.P., Sousa, A.A., Walton, R.T. et al. (2019). Engineered CRISPR‐Cas12a variants with increased activities and improved targeting ranges for gene, epigenetic and base editing. Nat. Biotechnol. 37: 276–282.
106 Klompe, S.E., Vo, P.L.H., Halpin‐Healy, T.S., and Sternberg, S.H. (2019). Transposon‐encoded CRISPR‐Cas systems direct RNA‐guided DNA integration. Nature 571: 219–225.
107 Komor, A.C., Kim, Y.B., Packer, M.S. et al. (2016). Programmable editing of a target base in genomic DNA without double‐stranded DNA cleavage. Nature 533: 420–424.
108 Konermann, S., Lotfy, P., Brideau, N.J. et al. (2018). Transcriptome engineering with RNA‐targeting Type VI‐D CRISPR effectors. Cell 173: 665–676. e14.
109 Koonin, E.V. and Makarova, K.S. (2019). Origins and evolution of CRISPR‐Cas systems. Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 374: 20180087.
110 Kosicki, M., Tomberg, K., and Bradley, A. (2018). Repair of double‐strand breaks induced by CRISPR‐Cas9 leads to large deletions and complex rearrangements. Nat. Biotechnol. 36: 765–771.
111 Kunin, V., Sorek, R., and Hugenholtz, P. (2007). Evolutionary conservation of sequence and secondary structures in CRISPR repeats. Genome Biol. 8: R61.
112 Lee, H., Zhou, Y., Taylor, D.W., and Sashital, D.G. (2018). Cas4‐Dependent Prespacer Processing Ensures High‐Fidelity Programming of CRISPR Arrays. Mol. Cell 70: 48–59. e5.
113 Lee, H., Dhingra, Y., and Sashital, D.G. (2019). The Cas4‐Cas1‐Cas2 complex mediates precise prespacer processing during CRISPR adaptation. elife 8.
114 Leenay, R.T., Maksimchuk, K.R., Slotkowski, R.A. et al. (2016). Identifying and visualizing functional PAM diversity across CRISPR‐Cas systems. Mol. Cell 62: 137–147.
115 Levy, A., Goren, M.G., Yosef, I. et al. (2015). CRISPR adaptation biases explain preference for acquisition of foreign DNA. Nature 520: 505–510.
116 Li, Y., Pan, S., Zhang, Y. et al. (2016). Harnessing Type I and Type III CRISPR‐Cas systems for genome editing. Nucleic Acids Res. 44: e34.
117 Li, S., Li, J., Zhang, J. et al. (2018a). Synthesis‐dependent repair of Cpf1‐induced double
