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 strand DNA breaks enables targeted gene replacement in rice. J. Exp. Bot. 69: 4715–4721.
118 Li, S.Y., Cheng, Q.X., Wang, J.M. et al. (2018b). CRISPR‐Cas12a‐assisted nucleic acid detection. Cell Discov. 4: 20.
119 Li, L., Li, S., Wu, N. et al. (2019a). HOLMESv2: a CRISPR‐Cas12b‐assisted platform for nucleic acid detection and DNA methylation quantitation. ACS Synth. Biol. 8: 2228–2237.
120 Li, Y., Li, S., Wang, J., and Liu, G. (2019b). CRISPR/Cas Systems towards Next‐generation biosensing. Trends Biotechnol. 37: 730–743.
121 Lillestol, R.K., Redder, P., Garrett, R.A., and Brugger, K. (2006). A putative viral defence mechanism in archaeal cells. Archaea 2: 59–72.
122 Liu, X.S., Wu, H., Ji, X. et al. (2016). Editing DNA methylation in the mammalian genome. Cell 167: 233–247. e17.
123 Liu, L., Chen, P., Wang, M. et al. (2017a). C2c1‐sgRNA complex structure reveals RNA‐guided DNA cleavage mechanism. Mol. Cell 65: 310–322.
124 Liu, L., Li, X., Ma, J. et al. (2017b). The molecular architecture for RNA‐guided RNA cleavage by Cas13a. Cell 170: 714–726. e10.
125 Liu, L., Li, X., Wang, J. et al. (2017c). Two distant catalytic sites are responsible for C2c2 RNase activities. Cell 168: 121–134. e12.
126 Liu, T.Y., Iavarone, A.T., and Doudna, J.A. (2017d). RNA and DNA targeting by a reconstituted thermus thermophilus Type III‐A CRISPR‐Cas system. PLoS One 12: e0170552.
127 Liu, J.J., Orlova, N., Oakes, B.L. et al. (2019a). CasX enzymes comprise a distinct family of RNA‐guided genome editors. Nature 566: 218–223.
128 Liu, T.Y., Liu, J.J., Aditham, A.J. et al. (2019b). Target preference of Type III‐A CRISPR‐Cas complexes at the transcription bubble. Nat. Commun. 10: 3001.
129 Lovett, S.T. (2011). The DNA exonucleases of Escherichia coli. EcoSal Plus 4.
130 Ma, E., Harrington, L.B., O'connell, M.R. et al. (2015). Single‐stranded DNA cleavage by Divergent CRISPR‐Cas9 enzymes. Mol. Cell 60: 398–407.
131 Magadan, A.H., Dupuis, M.E., Villion, M., and Moineau, S. (2012). Cleavage of phage DNA by the streptococcus thermophilus CRISPR3‐Cas system. PLoS One 7: e40913.
132 Maji, B., Moore, C.L., Zetsche, B. et al. (2017). Multidimensional chemical control of CRISPR‐Cas9. Nat. Chem. Biol. 13: 9–11.
133 Makarova, K.S., Grishin, N.V., Shabalina, S.A. et al. (2006). A putative RNA‐interference‐based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biol. Direct 1: 7.
134 Makarova, K.S., Wolf, Y.I., Iranzo, J. et al. (2019). Evolutionary classification of CRISPR–Cas systems: a burst of class 2 and derived variants. Nat. Rev. Microbiol. 18: 67–83.
135 Mali, P., Yang, L., Esvelt, K.M. et al. (2013). RNA‐guided human genome engineering via Cas9. Science 339: 823–826.
136 Maresca, M., Lin, V.G., Guo, N., and Yang, Y. (2013). Obligate ligation‐gated recombination (ObLiGaRe): custom‐designed nuclease‐mediated targeted integration through nonhomologous end joining. Genome Res. 23: 539–546.
137 Marino, N.D., Pinilla‐Redondo, R., Csorgo, B., and Bondy‐Denomy, J. (2020). Anti‐CRISPR protein applications: natural brakes for CRISPR‐Cas technologies. Nat. Methods 17: 471–479.
138 Marraffini, L.A. and Sontheimer, E.J. (2008). CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. Science 322: 1843–1845.
139 Mcginn, J. and Marraffini, L.A. (2016). CRISPR‐Cas systems optimize their immune response by specifying the site of spacer integration. Mol. Cell 64: 616–623.
140 Meeske, A.J., Nakandakari‐Higa, S., and Marraffini, L.A. (2019). Cas13‐induced cellular dormancy prevents the rise of CRISPR‐resistant bacteriophage. Nature 570: 241–245.
141 Mekler, V., Minakhin, L., and Severinov, K. (2017). Mechanism of duplex DNA destabilization by RNA‐guided Cas9 nuclease during target interrogation. Proc. Natl. Acad. Sci. U. S. A. 114: 5443–5448.
142 Miller, S.M., Wang, T., Randolph, P.B. et al. (2020). Continuous evolution of SpCas9 variants compatible with non‐G PAMs. Nat. Biotechnol. 38: 471–481.
143 Ming, M., Ren, Q., Pan, C. et al. (2020). CRISPR‐Cas12b enables efficient plant genome engineering. Nat. Plants 6: 202–208.
144 Mojica, F.J., Diez‐Villasenor, C., Soria, E., and Juez, G. (2000). Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria. Mol. Microbiol. 36: 244–246.
145 Mojica, F.J., Diez‐Villasenor, C., Garcia‐Martinez, J., and Soria, E. (2005). Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J. Mol. Evol. 60: 174–182.
146 Mojica, F.J.M., Diez‐Villasenor, C., Garcia‐Martinez, J., and Almendros, C. (2009). Short motif sequences determine the targets of the prokaryotic CRISPR defence system. Microbiol. (Reading) 155: 733–740.
147 Moreno‐Mateos, M.A., Fernandez, J.P., Rouet, R. et al. (2017). CRISPR‐Cpf1 mediates efficient homology‐directed repair and temperature‐controlled genome editing. Nat. Commun. 8: 2024.
148 Morisaka, H., Yoshimi, K., Okuzaki, Y. et al. (2019). CRISPR‐Cas3 induces broad and unidirectional genome editing in human cells. Nat. Commun. 10: 5302.
149 Mulepati, S., Heroux, A., and Bailey, S. (2014). Structural biology. Crystal structure of a CRISPR RNA‐guided surveillance complex bound to a ssDNA target. Science 345: 1479–1484.
150 Muller, M., Lee, C.M., Gasiunas, G. et al. (2016). Streptococcus thermophilus CRISPR‐Cas9 systems enable specific editing of the human genome. Mol. Ther. 24: 636–644.
151 Myhrvold, C., Freije, C.A., Gootenberg, J.S. et al. (2018). Field‐deployable viral diagnostics using CRISPR‐Cas13. Science 360: 444–448.
152 Nakata, A., Amemura, M., and Makino, K. (1989). Unusual nucleotide arrangement with repeated sequences in the Escherichia coli K‐12 chromosome. J. Bacteriol. 171: 3553–3556.
153 Nam, K.I.H., Haitjema, C., Liu, X. et al. (2012). Cas5d protein processes pre‐crRNA and assembles into a cascade‐like interference complex in subtype I‐C/Dvulg CRISPR‐Cas system. Structure 20: 1574–1584.
154 Newire, E., Aydin, A., Juma, S. et al. (2020). Identification of a Type IV‐A CRISPR‐Cas system located exclusively on IncHI1B/IncFIB plasmids in enterobacteriaceae. Front. Microbiol. 11: 1937.
155 Niewoehner, O., Garcia‐Doval, C., Rostol, J.T. et al. (2017). Type III CRISPR‐Cas systems produce cyclic oligoadenylate second messengers. Nature 548: 543–548.
156 Nihongaki, Y., Kawano, F., Nakajima, T., and Sato, M. (2015). Photoactivatable CRISPR‐Cas9 for optogenetic genome editing. Nat. Biotechnol. 33: 755–760.
157 Nishimasu, H., Shi, X., Ishiguro, S. et al. (2018). Engineered CRISPR‐Cas9 nuclease with expanded targeting space. Science 361: 1259–1262.
158 Nunez, J.K., Kranzusch, P.J., Noeske, J. et al. (2014). Cas1‐Cas2 complex formation mediates spacer acquisition during CRISPR‐Cas adaptive immunity. Nat. Struct. Mol. Biol. 21: 528–534.
159 Nunez, J.K., Harrington, L.B., Kranzusch, P.J. et al. (2015). Foreign DNA capture during CRISPR‐Cas adaptive immunity. Nature 527: 535–538.
160 Nuñez, J.K., Lee, A.S.Y., Engelman, A., and Doudna, J.A. (2015). Integrase‐mediated