- Smith, H. O. & Wilcox, K. W. A restriction enzyme from Hemophilus influenzae. I. Purification and general properties. J. Mol. Biol. 51, 379–391 (1970).
Article PubMed CAS Google Scholar
- Kelly, T. J. Jr. & Smith, H. O. A restriction enzyme from Hemophilus influenzae. II. J. Mol. Biol. 51, 393–409 (1970).
Article PubMed CAS Google Scholar
- Danna, K. & Nathans, D. Specific cleavage of simian virus 40 DNA by restriction endonuclease of Hemophilus influenzae. Proc. Natl Acad. Sci. USA 68, 2913–2917 (1971).
Article ADS PubMed PubMed Central CAS Google Scholar
- Rothstein, R. J. One-step gene disruption in yeast. Methods Enzymol. 101, 202–211 (1983).
Article PubMed CAS Google Scholar
- Smithies, O., Gregg, R. G., Boggs, S. S., Koralewski, M. A. & Kucherlapati, R. S. Insertion of DNA sequences into the human chromosomal beta-globin locus by homologous recombination. Nature 317, 230–234 (1985).
Article ADS PubMed CAS Google Scholar
- Thomas, K. R., Folger, K. R. & Capecchi, M. R. High frequency targeting of genes to specific sites in the mammalian genome. Cell 44, 419–428 (1986).
Article PubMed CAS Google Scholar
- Capecchi, M. R. Altering the genome by homologous recombination. Science 244, 1288–1292 (1989).
Article ADS PubMed CAS Google Scholar
- Lin, F. L., Sperle, K. & Sternberg, N. Recombination in mouse L cells between DNA introduced into cells and homologous chromosomal sequences. Proc. Natl Acad. Sci. USA 82, 1391–1395 (1985).
Article ADS PubMed PubMed Central CAS Google Scholar
- Rudin, N., Sugarman, E. & Haber, J. E. Genetic and physical analysis of double-strand break repair and recombination in Saccharomyces cerevisiae. Genetics 122, 519–534 (1989).
PubMed PubMed Central CAS Google Scholar
- Rouet, P., Smih, F. & Jasin, M. Introduction of double-strand breaks into the genome of mouse cells by expression of a rare-cutting endonuclease. Mol. Cell. Biol. 14, 8096–8106 (1994).
Article PubMed PubMed Central CAS Google Scholar
- Jeggo, P. A. DNA breakage and repair. Adv. Genet. 38, 185–218 (1998).
PubMed CAS Google Scholar
- Sussman, D. et al. Isolation and characterization of new homing endonuclease specificities at individual target site positions. J. Mol. Biol. 342, 31–41 (2004).
Article PubMed CAS Google Scholar
- Seligman, L. M. et al. Mutations altering the cleavage specificity of a homing endonuclease. Nucleic Acids Res. 30, 3870–3879 (2002).
Article PubMed PubMed Central CAS Google Scholar
- Rosen, L. E. et al. Homing endonuclease I-CreI derivatives with novel DNA target specificities. Nucleic Acids Res. 34, 4791–4800 (2006).
Article ADS PubMed PubMed Central CAS Google Scholar
- Klug, A. & Rhodes, D. Zinc fingers: a novel protein fold for nucleic acid recognition. Cold Spring Harb. Symp. Quant. Biol. 52, 473–482 (1987).
Article PubMed CAS Google Scholar
- Kim, Y. G., Cha, J. & Chandrasegaran, S. Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc. Natl Acad. Sci. USA 93, 1156–1160 (1996).
Article ADS PubMed PubMed Central CAS Google Scholar
- Bibikova, M. et al. Stimulation of homologous recombination through targeted cleavage by chimeric nucleases. Mol. Cell. Biol. 21, 289–297 (2001).
Article PubMed PubMed Central CAS Google Scholar
- Porteus, M. H. & Baltimore, D. Chimeric nucleases stimulate gene targeting in human cells. Science 300, 763 (2003).
Article PubMed Google Scholar
- Urnov, F. D. et al. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 435, 646–651 (2005).
Article ADS PubMed CAS Google Scholar
- Miller, J. C. et al. An improved zinc-finger nuclease architecture for highly specific genome editing. Nat. Biotechnol. 25, 778–785 (2007).
Article PubMed CAS Google Scholar
- Urnov, F. D., Rebar, E. J., Holmes, M. C., Zhang, H. S. & Gregory, P. D. Genome editing with engineered zinc finger nucleases. Nat. Rev. Genet. 11, 636–646 (2010).
Article PubMed CAS Google Scholar
- Boch, J. et al. Breaking the code of DNA binding specificity of TAL-type III effectors. Science 326, 1509–1512 (2009).
Article ADS PubMed CAS Google Scholar
- Moscou, M. J. & Bogdanove, A. J. A simple cipher governs DNA recognition by TAL effectors. Science 326, 1501 (2009).
Article ADS PubMed CAS Google Scholar
- Christian, M. et al. Targeting DNA double-strand breaks with TAL effector nucleases. Genetics 186, 757–761 (2010).
Article PubMed PubMed Central CAS Google Scholar
- Zhang, F. et al. Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription. Nat. Biotechnol. 29, 149–153 (2011).
Article PubMed PubMed Central CAS Google Scholar
- Miller, J. C. et al. A TALE nuclease architecture for efficient genome editing. Nat. Biotechnol. 29, 143–148 (2011).
Article PubMed CAS Google Scholar
- Li, T. et al. Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes. Nucleic Acids Res. 39, 6315–6325 (2011).
Article ADS PubMed PubMed Central CAS Google Scholar
- Jansen, R., Embden, J. D., Gaastra, W. & Schouls, L. M. Identification of genes that are associated with DNA repeats in prokaryotes. Mol. Microbiol. 43, 1565–1575 (2002).
Article PubMed CAS Google Scholar
- Ishino, Y., Shinagawa, H., Makino, K., Amemura, M. & Nakata, A. 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 (1987).
Article PubMed PubMed Central CAS Google Scholar
- Mojica, F. J., Diez-Villasenor, C., Soria, E. & Juez, G. Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria. Mol. Microbiol. 36, 244–246 (2000).
Article PubMed CAS Google Scholar
- Mojica, F. J., Diez-Villasenor, C., Garcia-Martinez, J. & Soria, E. Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J. Mol. Evol. 60, 174–182 (2005).
Article ADS PubMed CAS Google Scholar
- Bolotin, A., Quinquis, B., Sorokin, A. & Ehrlich, S. D. Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology 151, 2551–2561 (2005).
Article PubMed CAS Google Scholar
- Pourcel, C., Salvignol, G. & Vergnaud, G. CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies. Microbiology 151, 653–663 (2005).
Article PubMed CAS Google Scholar
- Makarova, K. S., Grishin, N. V., Shabalina, S. A., Wolf, Y. I. & Koonin, E. V. 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 (2006).
Article PubMed PubMed Central CAS Google Scholar
- Barrangou, R. et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science 315, 1709–1712 (2007).
Article ADS PubMed CAS Google Scholar
- Brouns, S. J. et al. Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 321, 960–964 (2008).
Article ADS PubMed PubMed Central CAS Google Scholar
- Marraffini, L. A. & Sontheimer, E. J. CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. Science 322, 1843–1845 (2008).
Article ADS PubMed PubMed Central CAS Google Scholar
- Deveau, H. et al. Phage response to CRISPR-encoded resistance in Streptococcus thermophilus. J. Bacteriol. 190, 1390–1400 (2008).
Article PubMed CAS Google Scholar
- Garneau, J. E. et al. The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature 468, 67–71 (2010).
Article ADS PubMed CAS Google Scholar
- Deltcheva, E. et al. CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature 471, 602–607 (2011).
Article ADS PubMed PubMed Central CAS Google Scholar
- Sapranauskas, R. et al. The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli. Nucleic Acids Res. 39, 9275–9282 (2011).
Article PubMed PubMed Central CAS Google Scholar
- Jinek, M. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337, 816–821 (2012).
Article ADS PubMed CAS Google Scholar
- Gasiunas, G., Barrangou, R., Horvath, P. & Siksnys, V. Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc. Natl Acad. Sci. USA 109, E2579–E2586 (2012).
Article ADS PubMed PubMed Central Google Scholar
- Jinek, M. et al. RNA-programmed genome editing in human cells. Elife 2, e00471 (2013).
Article PubMed PubMed Central Google Scholar
- Cong, L. et al. Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819–823 (2013).
Article ADS PubMed PubMed Central CAS Google Scholar
- Mali, P. et al. RNA-guided human genome engineering via Cas9. Science 339, 823–826 (2013).
Article ADS PubMed PubMed Central CAS Google Scholar
- Haft, D. H., Selengut, J., Mongodin, E. F. & Nelson, K. E. A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes. PLoS Comput. Biol. 1, e60 (2005).
Article ADS PubMed PubMed Central CAS Google Scholar
- Makarova, K. S. et al. Evolution and classification of the CRISPR-Cas systems. Nat. Rev. Microbiol. 9, 467–477 (2011).
Article PubMed CAS Google Scholar
- Koonin, E. V., Makarova, K. S. & Zhang, F. Diversity, classification and evolution of CRISPR-Cas systems. Curr. Opin. Microbiol. 37, 67–78 (2017).
Article PubMed CAS PubMed Central Google Scholar
- Yamano, T. et al. Crystal structure of Cpf1 in complex with guide RNA and target DNA. Cell 165, 949–962 (2016).
Article PubMed PubMed Central CAS Google Scholar
- Zetsche, B. et al. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell 163, 759–771 (2015).
Article PubMed PubMed Central CAS Google Scholar
- Fonfara, I., Richter, H., Bratovic, M., Le Rhun, A. & Charpentier, E. The CRISPR-associated DNA-cleaving enzyme Cpf1 also processes precursor CRISPR RNA. Nature 532, 517–521 (2016).
Article ADS PubMed CAS Google Scholar
- Hou, Z. et al. Efficient genome engineering in human pluripotent stem cells using Cas9 from Neisseria meningitidis. Proc. Natl Acad. Sci. USA 110, 15644–15649 (2013).
Article ADS PubMed PubMed Central CAS Google Scholar
- Ran, F. A. et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature 520, 186–191 (2015).
Article ADS PubMed PubMed Central CAS Google Scholar
- Friedland, A. E. et al. Characterization of Staphylococcus aureus Cas9: a smaller Cas9 for all-in-one adeno-associated virus delivery and paired nickase applications. Genome Biol. 16, 257 (2015).
Article PubMed PubMed Central CAS Google Scholar
- Kim, E. et al. In vivo genome editing with a small Cas9 orthologue derived from Campylobacter jejuni. Nat. Commun. 8, 14500 (2017).
Article ADS PubMed PubMed Central CAS Google Scholar
- Mojica, F. J., Diez-Villasenor, C., Garcia-Martinez, J. & Almendros, C. Short motif sequences determine the targets of the prokaryotic CRISPR defence system. Microbiology 155, 733–740 (2009).
Article PubMed CAS Google Scholar
- Kleinstiver, B. P. et al. Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition. Nat. Biotechnol. 33, 1293–1298 (2015).
Article PubMed PubMed Central CAS Google Scholar
- Kleinstiver, B. P. et al. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature 523, 481–485 (2015).
Article ADS PubMed PubMed Central CAS Google Scholar
- Hirano, H. et al. Structure and engineering of Francisella novicida Cas9. Cell 164, 950–961 (2016).
Article PubMed PubMed Central CAS Google Scholar
- Hsu, P. D. et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat. Biotechnol. 31, 827–832 (2013).
Article PubMed PubMed Central CAS Google Scholar
- Mali, P. et al. CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat. Biotechnol. 31, 833–838 (2013).
Article PubMed PubMed Central CAS Google Scholar
- Pattanayak, V. et al. High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity. Nat. Biotechnol. 31, 839–843 (2013).
Article PubMed PubMed Central CAS Google Scholar
- Fu, Y. et al. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat. Biotechnol. 31, 822–826 (2013).
Article PubMed PubMed Central CAS Google Scholar
- Cho, S. W. et al. Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases. Genome Res. 24, 132–141 (2014).
Article PubMed PubMed Central CAS Google Scholar
- Kuscu, C., Arslan, S., Singh, R., Thorpe, J. & Adli, M. Genome-wide analysis reveals characteristics of off-target sites bound by the Cas9 endonuclease. Nat. Biotechnol. 32, 677–683 (2014).
Article PubMed CAS Google Scholar
- Wu, X. et al. Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells. Nat. Biotechnol. 32, 670–676 (2014).
Article PubMed PubMed Central CAS Google Scholar
- Singh, R., Kuscu, C., Quinlan, A., Qi, Y. & Adli, M. Cas9-chromatin binding information enables more accurate CRISPR off-target prediction. Nucleic Acids Res. 43, e118 (2015).
Article PubMed PubMed Central CAS Google Scholar
- Crosetto, N. et al. Nucleotide-resolution DNA double-strand break mapping by next-generation sequencing. Nat. Methods 10, 361–365 (2013).
Article PubMed PubMed Central CAS Google Scholar
- Tsai, S. Q. et al. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat. Biotechnol. 33, 187–197 (2015).
Article PubMed CAS Google Scholar
- Kim, D. et al. Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells. Nat. Methods 12, 237–243 (2015).
Article PubMed CAS 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 ADS PubMed PubMed Central CAS Google Scholar
- Slaymaker, I. M. et al. Rationally engineered Cas9 nucleases with improved specificity. Science 351, 84–88 (2016).
Article ADS PubMed CAS Google Scholar
- Lin, S., Staahl, B. T., Alla, R. K. & Doudna, J. A. Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery. Elife 3, e04766 (2014).
Article PubMed PubMed Central Google Scholar
- Kim, S., Kim, D., Cho, S. W., Kim, J. & Kim, J. S. Highly efficient RNA-guided genome editing in human cells via delivery of purified Cas9 ribonucleoproteins. Genome Res. 24, 1012–1019 (2014).
Article PubMed PubMed Central CAS Google Scholar
- Ran, F. A. et al. Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 8, 2281–2308 (2013).
Article PubMed PubMed Central CAS Google Scholar
- Guilinger, J. P., Thompson, D. B. & Liu, D. R. Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nat. Biotechnol. 32, 577–582 (2014).
Article PubMed PubMed Central CAS Google Scholar
- Tsai, S. Q. et al. Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing. Nat. Biotechnol. 32, 569–576 (2014).
Article PubMed PubMed Central CAS Google Scholar
- Dow, L. E. et al. Inducible in vivo genome editing with CRISPR-Cas9. Nat. Biotechnol. 33, 390–394 (2015).
Article PubMed PubMed Central CAS Google Scholar
- Nihongaki, Y., Kawano, F., Nakajima, T. & Sato, M. Photoactivatable CRISPR-Cas9 for optogenetic genome editing. Nat. Biotechnol. 33, 755–760 (2015).
Article PubMed CAS Google Scholar
- Hemphill, J., Borchardt, E. K., Brown, K., Asokan, A. & Deiters, A. Optical control of CRISPR/Cas9 gene editing. J. Am. Chem. Soc. 137, 5642–5645 (2015).
Article PubMed PubMed Central CAS Google Scholar
- Oakes, B. L. et al. Profiling of engineering hotspots identifies an allosteric CRISPR-Cas9 switch. Nat. Biotechnol. 34, 646–651 (2016).
Article PubMed PubMed Central CAS Google Scholar
- Fu, Y., Sander, J. D., Reyon, D., Cascio, V. M. & Joung, J. K. Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat. Biotechnol. 32, 279–284 (2014).
Article PubMed PubMed Central CAS Google Scholar
- Tang, W., Hu, J. H. & Liu, D. R. Aptazyme-embedded guide RNAs enable ligand-responsive genome editing and transcriptional activation. Nat. Commun. 8, 15939 (2017).
Article ADS PubMed PubMed Central CAS Google Scholar
- Qi, L. S. et al. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell 152, 1173–1183 (2013).
Article PubMed PubMed Central CAS Google Scholar
- Nishimasu, H. et al. Crystal structure of Cas9 in complex with guide RNA and target DNA. Cell 156, 935–949 (2014).
Article PubMed PubMed Central CAS 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 ADS PubMed PubMed Central CAS 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 ADS PubMed PubMed Central CAS Google Scholar
- Nishida, K. et al. Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems. Science 353, https://doi.org/10.1126/science.aaf8729 (2016).
- Kuscu, C. et al. CRISPR-STOP: Gene silencing through base editing-induced nonsense mutations. Nat. Methods 14, 710–712 (2017).
- Billon, P. et al. CRISPR-mediated base editing enables efficient disruption of eukaryotic genes through induction of STOP codons. Mol. Cell. 67, 1068–1079 e1064 (2017).
Article PubMed CAS PubMed Central Google Scholar
- Hess, G. T. et al. Directed evolution using dCas9-targeted somatic hypermutation in mammalian cells. Nat. Methods 13, 1036–1042 (2016).
- Ma, Y. et al. Targeted AID-mediated mutagenesis (TAM) enables efficient genomic diversification in mammalian cells. Nat. Methods 13, 1029–1035 (2016).
Article PubMed CAS Google Scholar
- Kuscu, C. & Adli, M. CRISPR-Cas9-AID base editor is a powerful gain-of-function screening tool. Nat. Methods 13, 983–984 (2016).
- Gilbert, L. A. et al. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154, 442–451 (2013).
Article PubMed PubMed Central CAS Google Scholar
- Urrutia, R. KRAB-containing zinc-finger repressor proteins. Genome Biol. 4, 231 (2003).
Article PubMed PubMed Central Google Scholar
- Friedman, J. R. et al. KAP-1, a novel corepressor for the highly conserved KRAB repression domain. Genes Dev. 10, 2067–2078 (1996).
Article PubMed CAS Google Scholar
- Groner, A. C. et al. KRAB-zinc finger proteins and KAP1 can mediate long-range transcriptional repression through heterochromatin spreading. PLoS Genet. 6, e1000869 (2010).
Article PubMed PubMed Central CAS Google Scholar
- Thakore, P. I. et al. Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements. Nat. Methods 12, 1143–1149 (2015).
Article PubMed PubMed Central CAS Google Scholar
- Maeder, M. L. et al. CRISPR RNA-guided activation of endogenous human genes. Nat. Methods 10, 977–979 (2013).
Article PubMed PubMed Central CAS Google Scholar
- Perez-Pinera, P. et al. RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat. Methods 10, 973–976 (2013).
Article PubMed PubMed Central CAS Google Scholar
- Wysocka, J. & Herr, W. The herpes simplex virus VP16-induced complex: the makings of a regulatory switch. Trends Biochem. Sci. 28, 294–304 (2003).
Article PubMed CAS Google Scholar
- Cheng, A. W. et al. Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system. Cell. Res. 23, 1163–1171 (2013).
Article PubMed PubMed Central CAS Google Scholar
- Chavez, A. et al. Highly efficient Cas9-mediated transcriptional programming. Nat. Methods 12, 326–328 (2015).
Article PubMed PubMed Central CAS Google Scholar
- Hardwick, J. M., Tse, L., Applegren, N., Nicholas, J. & Veliuona, M. A. The Epstein-Barr virus R transactivator (Rta) contains a complex, potent activation domain with properties different from those of VP16. J. Virol. 66, 5500–5508 (1992).
PubMed PubMed Central CAS Google Scholar
- Sugiyama, T. & Nakada, D. Translational control of bacteriophage MS2 RNA cistrons by MS2 coat protein: affinity and specificity of the interaction of MS2 coat protein with MS2 RNA. J. Mol. Biol. 48, 349–355 (1970).
Article PubMed CAS Google Scholar
- Peabody, D. S. The RNA binding site of bacteriophage MS2 coat protein. EMBO J. 12, 595–600 (1993).
Article PubMed PubMed Central CAS Google Scholar
- Zalatan, J. G. et al. Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds. Cell 160, 339–350 (2015).
Article PubMed CAS Google Scholar
- Konermann, S. et al. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 517, 583–588 (2015).
Article ADS PubMed CAS Google Scholar
- Tanenbaum, M. E., Gilbert, L. A., Qi, L. S., Weissman, J. S. & Vale, R. D. A protein-tagging system for signal amplification in gene expression and fluorescence imaging. Cell 159, 635–646 (2014)
- Chavez, A. et al. Comparison of Cas9 activators in multiple species. Nat. Methods 13, 563–567 (2016).
Article PubMed PubMed Central CAS Google Scholar
- Nihongaki, Y., Yamamoto, S., Kawano, F., Suzuki, H. & Sato, M. CRISPR-Cas9-based photoactivatable transcription system. Chem. Biol. 22, 169–174 (2015).
Article PubMed CAS Google Scholar
- Polstein, L. R. & Gersbach, C. A. A light-inducible CRISPR-Cas9 system for control of endogenous gene activation. Nat. Chem. Biol. 11, 198–200 (2015).
Article PubMed PubMed Central CAS Google Scholar
- Zetsche, B., Volz, S. E. & Zhang, F. A split-Cas9 architecture for inducible genome editing and transcription modulation. Nat. Biotechnol. 33, 139–142 (2015).
Article PubMed CAS Google Scholar
- Gao, Y. et al. Complex transcriptional modulation with orthogonal and inducible dCas9 regulators. Nat. Methods 13, 1043–1049 (2016).
Article PubMed PubMed Central CAS Google Scholar
- Ptashne, M. On the use of the word ‘epigenetic’. Curr. Biol. 17, R233–R236 (2007).
Article PubMed CAS Google Scholar
- Greally, J. M. A user’s guide to the ambiguous word ‘epigenetics’. Nat. Rev. Mol. Cell. Biol. 19, 207–208 (2018).
Article PubMed CAS Google Scholar
- Consortium, E. P. et al. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012).
Article ADS CAS Google Scholar
- Bernstein, B. E. et al. The NIH Roadmap Epigenomics Mapping Consortium. Nat. Biotechnol. 28, 1045–1048 (2010).
Article PubMed PubMed Central CAS Google Scholar
- Holliday, R. & Pugh, J. E. DNA modification mechanisms and gene activity during development. Science 187, 226–232 (1975).
Article ADS PubMed CAS Google Scholar
- Riggs, A. D. X inactivation, differentiation, and DNA methylation. Cytogenet. Cell Genet. 14, 9–25 (1975).
Article PubMed CAS Google Scholar
- Razin, A. & Riggs, A. D. DNA methylation and gene function. Science 210, 604–610 (1980).
Article ADS PubMed CAS Google Scholar
- Okano, M., Bell, D. W., Haber, D. A. & Li, E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99, 247–257 (1999).
Article PubMed CAS Google Scholar
- Kaminskas, E., Farrell, A. T., Wang, Y. C., Sridhara, R. & Pazdur, R. FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist 10, 176–182 (2005).
Article PubMed CAS Google Scholar
- Liu, X. S. et al. Editing DNA methylation in the mammalian genome. Cell 167, 233–247.e17 (2016).
Article PubMed PubMed Central CAS Google Scholar
- Amabile, A. et al. Inheritable silencing of endogenous genes by hit-and-run targeted epigenetic editing. Cell 167, 219–232.e214 (2016).
Article PubMed PubMed Central CAS Google Scholar
- Vojta, A. et al. Repurposing the CRISPR-Cas9 system for targeted DNA methylation. Nucleic Acids Res. 44, 5615–5628 (2016).
Article PubMed PubMed Central CAS Google Scholar
- McDonald, J. I. et al. Reprogrammable CRISPR/Cas9-based system for inducing site-specific DNA methylation. Biol. Open 5, 866–874 (2016).
Article PubMed PubMed Central CAS Google Scholar
- Lei, Y. et al. Targeted DNA methylation in vivo using an engineered dCas9-MQ1 fusion protein. Nat. Commun. 8, 16026 (2017).
Article ADS PubMed PubMed Central CAS Google Scholar
- Xiong, T. et al. Targeted DNA methylation in human cells using engineered dCas9-methyltransferases. Sci. Rep. 7, 6732 (2017).
Article ADS PubMed PubMed Central CAS Google Scholar
- Morita, S. et al. Targeted DNA demethylation in vivo using dCas9-peptide repeat and scFv-TET1 catalytic domain fusions. Nat. Biotechnol. 34, 1060–1065 (2016).
Article PubMed CAS Google Scholar
- Xu, X. et al. A CRISPR-based approach for targeted DNA demethylation. Cell Discov. 2, 16009 (2016).
Article PubMed PubMed Central CAS Google Scholar
- Stepper, P. et al. Efficient targeted DNA methylation with chimeric dCas9-Dnmt3a-Dnmt3L methyltransferase. Nucleic Acids Res. 45, 1703–1713 (2017).
Article PubMed CAS Google Scholar
- Galonska, C. et al. Genome-wide tracking of dCas9-methyltransferase footprints. Nat. Commun. 9, 597 (2018).
Article ADS PubMed PubMed Central CAS Google Scholar
- Kohli, R. M. & Zhang, Y. TET enzymes, TDG and the dynamics of DNA demethylation. Nature 502, 472–479 (2013).
Article ADS PubMed PubMed Central CAS Google Scholar
- Choudhury, S. R., Cui, Y., Lubecka, K., Stefanska, B. & Irudayaraj, J. CRISPR-dCas9 mediated TET1 targeting for selective DNA demethylation at BRCA1 promoter. Oncotarget 7, 46545–46556 (2016).
PubMed PubMed Central Google Scholar
- Thurman, R. E. et al. The accessible chromatin landscape of the human genome. Nature 489, 75–82 (2012).
Article ADS PubMed PubMed Central CAS Google Scholar
- Strahl, B. D. & Allis, C. D. The language of covalent histone modifications. Nature 403, 41–45 (2000).
Article ADS PubMed CAS Google Scholar
- Kearns, N. A. et al. Functional annotation of native enhancers with a Cas9-histone demethylase fusion. Nat. Methods 12, 401–403 (2015).
Article PubMed PubMed Central CAS Google Scholar
- Shi, Y. et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119, 941–953 (2004).
Article PubMed CAS Google Scholar
- Mendenhall, E. M. et al. Locus-specific editing of histone modifications at endogenous enhancers. Nat. Biotechnol. 31, 1133–1136 (2013).
Article PubMed PubMed Central CAS Google Scholar
- Hilton, I. B. et al. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nat. Biotechnol. 33, 510–517 (2015).
Article PubMed PubMed Central CAS Google Scholar
- Cano-Rodriguez, D. et al. Writing of H3K4Me3 overcomes epigenetic silencing in a sustained but context-dependent manner. Nat. Commun. 7, 12284 (2016).
Article ADS PubMed PubMed Central CAS Google Scholar
- Kwon, D. Y., Zhao, Y. T., Lamonica, J. M. & Zhou, Z. Locus-specific histone deacetylation using a synthetic CRISPR-Cas9-based HDAC. Nat. Commun. 8, 15315 (2017).
Article ADS PubMed PubMed Central CAS Google Scholar
- Braun, S. M. G. et al. Rapid and reversible epigenome editing by endogenous chromatin regulators. Nat. Commun. 8, 560 (2017).
Article ADS PubMed PubMed Central CAS Google Scholar
- Klann, T. S. et al. CRISPR-Cas9 epigenome editing enables high-throughput screening for functional regulatory elements in the human genome. Nat. Biotechnol. 35, 561–568 (2017).
Article PubMed PubMed Central CAS Google Scholar
- Chakraborty, S. et al. A CRISPR/Cas9-based system for reprogramming cell lineage specification. Stem Cell Rep. 3, 940–947 (2014).
Article CAS Google Scholar
- Balboa, D. et al. Conditionally stabilized dCas9 activator for controlling gene expression in human cell reprogramming and differentiation. Stem Cell Rep. 5, 448–459 (2015).
Article CAS Google Scholar
- Xiong, K. et al. Generation of induced pluripotent stem cells (iPSCs) stably expressing CRISPR-based synergistic activation mediator (SAM). Stem Cell Res. 17, 665–669 (2016).
Article PubMed CAS Google Scholar
- Bialek, J. K. et al. Targeted HIV-1 latency reversal using CRISPR/Cas9-derived transcriptional activator systems. PLoS ONE 11, e0158294 (2016).
Article PubMed PubMed Central CAS Google Scholar
- Nishimura, K., Fukagawa, T., Takisawa, H., Kakimoto, T. & Kanemaki, M. An auxin-based degron system for the rapid depletion of proteins in nonplant cells. Nat. Methods 6, 917–922 (2009).
Article PubMed CAS Google Scholar
- Dixon, J. R. et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376–380 (2012).
Article ADS PubMed PubMed Central CAS Google Scholar
- Bickmore, W. A. The spatial organization of the human genome. Annu. Rev. Genomics Hum. Genet. 14, 67–84 (2013).
Article PubMed CAS Google Scholar
- Meaburn, K. J., Misteli, T. & Soutoglou, E. Spatial genome organization in the formation of chromosomal translocations. Semin. Cancer Biol. 17, 80–90 (2007).
Article PubMed CAS Google Scholar
- Shachar, S., Voss, T. C., Pegoraro, G., Sciascia, N. & Misteli, T. Identification of gene positioning factors using high-throughput imaging mapping. Cell 162, 911–923 (2015).
Article PubMed PubMed Central CAS Google Scholar
- Lindhout, B. I. et al. Live cell imaging of repetitive DNA sequences via GFP-tagged polydactyl zinc finger proteins. Nucleic Acids Res. 35, e107 (2007).
Article PubMed PubMed Central CAS Google Scholar
- Miyanari, Y., Ziegler-Birling, C. & Torres-Padilla, M. E. Live visualization of chromatin dynamics with fluorescent TALEs. Nat. Struct. Mol. Biol. 20, 1321–1324 (2013).
Article PubMed CAS Google Scholar
- Chen, B. et al. Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell 155, 1479–1491 (2013).
Article PubMed PubMed Central CAS Google Scholar
- Ma, H. et al. Multicolor CRISPR labeling of chromosomal loci in human cells. Proc. Natl Acad. Sci. USA 112, 3002–3007 (2015).
Article ADS PubMed PubMed Central CAS Google Scholar
- Shao, S. et al. Long-term dual-color tracking of genomic loci by modified sgRNAs of the CRISPR/Cas9 system. Nucleic Acids Res. 44, e86 (2016).
Article PubMed PubMed Central CAS Google Scholar
- Wang, S., Su, J. H., Zhang, F. & Zhuang, X. An RNA-aptamer-based two-color CRISPR labeling system. Sci. Rep. 6, 26857 (2016).
Article ADS PubMed PubMed Central CAS Google Scholar
- Fu, Y. et al. CRISPR-dCas9 and sgRNA scaffolds enable dual-colour live imaging of satellite sequences and repeat-enriched individual loci. Nat. Commun. 7, 11707 (2016).
Article ADS PubMed PubMed Central CAS Google Scholar
- Ma, H. et al. Multiplexed labeling of genomic loci with dCas9 and engineered sgRNAs using CRISPRainbow. Nat. Biotechnol. 34, 528–530 (2016).
Article PubMed PubMed Central CAS Google Scholar
- Anton, T., Bultmann, S., Leonhardt, H. & Markaki, Y. Visualization of specific DNA sequences in living mouse embryonic stem cells with a programmable fluorescent CRISPR/Cas system. Nucleus 5, 163–172 (2014).
Article PubMed PubMed Central Google Scholar
- Qin, P. et al. Live cell imaging of low- and non-repetitive chromosome loci using CRISPR-Cas9. Nat. Commun. 8, 14725 (2017).
Article ADS PubMed PubMed Central CAS Google Scholar
- Deng, W. et al. Reactivation of developmentally silenced globin genes by forced chromatin looping. Cell 158, 849–860 (2014).
Article PubMed PubMed Central CAS Google Scholar
- Morgan, S. L. et al. Manipulation of nuclear architecture through CRISPR-mediated chromosomal looping. Nat. Commun. 8, 15993 (2017).
Article ADS PubMed PubMed Central CAS Google Scholar
- Liang, F. S., Ho, W. Q. & Crabtree, G. R. Engineering the ABA plant stress pathway for regulation of induced proximity. Sci. Signal. 4, rs2 (2011).
Article PubMed PubMed Central Google Scholar
- Hao, N., Shearwin, K. E. & Dodd, I. B. Programmable DNA looping using engineered bivalent dCas9 complexes. Nat. Commun. 8, 1628 (2017).
Article ADS PubMed PubMed Central CAS Google Scholar
- Shalem, O. et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343, 84–87 (2014).
Article ADS PubMed CAS Google Scholar
- Wang, T., Wei, J. J., Sabatini, D. M. & Lander, E. S. Genetic screens in human cells using the CRISPR-Cas9 system. Science 343, 80–84 (2014).
Article ADS PubMed CAS Google Scholar
- Koike-Yusa, H., Li, Y., Tan, E. P., Velasco-Herrera Mdel, C. & Yusa, K. Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library. Nat. Biotechnol. 32, 267–273 (2014).
Article PubMed CAS Google Scholar
- Doench, J. G. Am I ready for CRISPR? A user's guide to genetic screens. Nat. Rev. Genet. 19, 67–80 (2018).
Article PubMed CAS Google Scholar
- Brenner, S. Life sentences: Detective Rummage investigates. Genome. Biol. 9, 1013.1–1013.2 (2002).
- Hsu, P. D., Lander, E. S. & Zhang, F. Development and applications of CRISPR-Cas9 for genome engineering. Cell 157, 1262–1278 (2014).
Article PubMed PubMed Central CAS Google Scholar
- Pulecio, J., Verma, N., Mejia-Ramirez, E., Huangfu, D. & Raya, A. CRISPR/Cas9-based engineering of the epigenome. Cell Stem Cell 21, 431–447 (2017).
Article PubMed CAS Google Scholar
- Barrangou, R. & Horvath, P. A decade of discovery: CRISPR functions and applications. Nat. Microbiol. 2, 17092 (2017).
Article PubMed CAS Google Scholar
- Sander, J. D. & Joung, J. K. CRISPR-Cas systems for editing, regulating and targeting genomes. Nat. Biotechnol. 32, 347–355 (2014).
Article PubMed PubMed Central CAS Google Scholar
- Doudna, J. A. & Charpentier, E. Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 346, 1258096 (2014).
Article PubMed CAS Google Scholar
- Fellmann, C., Gowen, B. G., Lin, P. C., Doudna, J. A. & Corn, J. E. Cornerstones of CRISPR-Cas in drug discovery and therapy. Nat. Rev. Drug. Discov. 16, 89–100 (2017).
Article PubMed CAS Google Scholar
- Wang, H., La Russa, M. & Qi, L. S. CRISPR/Cas9 in genome editing and beyond. Annu. Rev. Biochem. 85, 227–264 (2016).
Article PubMed CAS Google Scholar
- Dunbar, C. E. et al. Gene therapy comes of age. Science 359, https://doi.org/10.1126/science.aan4672 (2018).
- Baltimore, D. et al. Biotechnology. A prudent path forward for genomic engineering and germline gene modification. Science 348, 36–38 (2015).
Article ADS PubMed PubMed Central CAS Google Scholar
- Gantz, V. M. & Bier, E. Genome editing. The mutagenic chain reaction: a method for converting heterozygous to homozygous mutations. Science 348, 442–444 (2015).
Article ADS PubMed PubMed Central CAS Google Scholar
- Gantz, V. M. et al. Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. Proc. Natl Acad. Sci. USA 112, E6736–E6743 (2015).
Article ADS PubMed PubMed Central CAS Google Scholar
- Hammond, A. et al. A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nat. Biotechnol. 34, 78–83 (2016).
Article PubMed CAS Google Scholar
- Oye, K. A. et al. Biotechnology. Regulating gene drives. Science 345, 626–628 (2014).
Article ADS PubMed CAS Google Scholar
- Esvelt, K. M., Smidler, A. L., Catteruccia, F. & Church, G. M. Concerning RNA-guided gene drives for the alteration of wild populations. Elife 3, https://doi.org/10.7554/eLife.03401 (2014).
- Charlesworth, C. T. et al. Identification of pre-existing adaptive immunity to Cas9 proteins in humans. BioArxhiv, https://doi.org/10.1101/243345 (2018).
- Moreno, A. M. et al. Exploring protein orthogonality in immune space: a case study with AAV and Cas9 orthologs. Preprint at https://www.biorxiv.org/content/early/2018/01/10/245985 (2018).