Strategies for precision modulation of gene expression by epigenome editing: An overview

Epigenetics and Chromatin

Volumn 8, Issue 1, 2015, Pages

  Laufer, Benjamin I ^a   Singh, Shiva M ^a  

^a UNIVERSITY OF WESTERN ONTARIO   (Canada)

Author keywords

CRISPR Cas9; dCas9; Functional genomics; Regulation of gene expression; Stem cells; Synthetic biology; Transcription Activator Like Effector (TALE); Zinc Finger

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR; CRISPR ASSOCIATED PROTEIN; CRISPR ASSOCIATED PROTEIN 9; TRANSCRIPTION ACTIVATOR LIKE EFFECTOR NUCLEASE; UNCLASSIFIED DRUG; ZINC FINGER NUCLEASE; ZINC FINGER PROTEIN;

BINDING AFFINITY; BIOTECHNOLOGY; DEACETYLATION; DNA BINDING; DNA METHYLATION; DNA SEQUENCE; EPIGENETICS; EPIGENOME EDITING; GENE EXPRESSION; GENE REPRESSION; GENETIC ENGINEERING; GENETIC TRANSCRIPTION; HISTONE DEMETHYLATION; HUMAN; PRIORITY JOURNAL; REVIEW; TRANSACTIVATION;

EID: 84941760719     PISSN: None     EISSN: 17568935     Source Type: Journal    
DOI: 10.1186/s13072-015-0023-7     Document Type: Review

References (125)

1. de Groote ML, Verschure PJ, Rots MG. Epigenetic Editing: targeted rewriting of epigenetic marks to modulate expression of selected target genes. Nucleic Acids Res. 2012;40(21):10596-613.
2. Jurkowski TP, Ravichandran M, Stepper P. Synthetic epigenetics-towards intelligent control of epigenetic states and cell identity. Clin Epigenetics. 2015;7(1):1-12.
3. Ramalingam S, Annaluru N, Chandrasegaran S. A CRISPR way to engineer the human genome. Genome Biol. 2013;14(2):107.
4. Gaj T, Gersbach CA, Barbas CF 3rd. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 2013;31(7):397-405.
5. Peng Y, Clark KJ, Campbell JM, Panetta MR, Guo Y, Ekker SC. Making designer mutants in model organisms. Development. 2014;141(21):4042-54.
6. Kim YG, Cha J, Chandrasegaran S. Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc Natl Acad Sci USA. 1996;93(3):1156-60.
7. Bibikova M, Carroll D, Segal DJ, Trautman JK, Smith J, Kim YG, Chandrasegaran S. Stimulation of homologous recombination through targeted cleavage by chimeric nucleases. Mol Cell Biol. 2001;21(1):289-97.
8. Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD. Genome editing with engineered zinc finger nucleases. Nat Rev Genet. 2010;11(9):636-46.
9. Liu J, Stormo GD. Context-dependent DNA recognition code for C2H2 zinc-finger transcription factors. Bioinformatics. 2008;24(17):1850-7.
10. Sanjana NE, Cong L, Zhou Y, Cunniff MM, Feng G, Zhang F. A transcription activator-like effector toolbox for genome engineering. Nat Protoc. 2012;7(1):171-92.
11. Sun N, Zhao H. Transcription activator-like effector nucleases (TALENs): a highly efficient and versatile tool for genome editing. Biotechnol Bioeng. 2013;110(7):1811-21.
12. Deng D, Yan C, Wu J, Pan X, Yan N. Revisiting the TALE repeat. Protein Cell. 2014;5(4):297-306.
13. Boch J, Scholze H, Schornack S, Landgraf A, Hahn S, Kay S, Lahaye T, Nickstadt A, Bonas U. Breaking the code of DNA binding specificity of TAL-type III effectors. Science. 2009;326(5959):1509-12.
14. Moscou MJ, Bogdanove AJ. A simple cipher governs DNA recognition by TAL effectors. Science. 2009;326(5959):1501.
15. Christian M, Cermak T, Doyle EL, Schmidt C, Zhang F, Hummel A, Bogdanove AJ, Voytas DF. Targeting DNA double-strand breaks with TAL effector nucleases. Genetics. 2010;186(2):757-61.
16. Morbitzer R, Romer P, Boch J, Lahaye T. Regulation of selected genome loci using de novo-engineered transcription activator-like effector (TALE)-type transcription factors. Proc Natl Acad Sci USA. 2010;107(50):21617-22.
17. Cong L, Zhou R, Kuo YC, Cunniff M, Zhang F. Comprehensive interrogation of natural TALE DNA-binding modules and transcriptional repressor domains. Nat Commun. 2012;3:968.
18. Reyon D, Maeder ML, Khayter C, Tsai SQ, Foley JE, Sander JD, Joung JK. Engineering customized TALE nucleases (TALENs) and TALE transcription factors by fast ligation-based automatable solid-phase high-throughput (FLASH) assembly. Curr Protoc Mol Biol. 2013;Chapter 12:Unit 12.16.
19. Maeder ML, Thibodeau-Beganny S, Sander JD, Voytas DF, Joung JK. Oligomerized pool engineering (OPEN): an 'open-source' protocol for making customized zinc-finger arrays. Nat Protoc. 2009;4(10):1471-501.
20. Reddy P, Ocampo A, Suzuki K, Luo J, Bacman SR, Williams SL, Sugawara A, Okamura D, Tsunekawa Y, Wu J, Lam D, Xiong X, Montserrat N, Esteban CR, Liu GH, Sancho-Martinez I, Manau D, Civico S, Cardellach F, Del Mar O'Callaghan M, Campistol J, Zhao H, Campistol JM, Moraes CT, Izpisua Belmonte JC. Selective elimination of mitochondrial mutations in the germline by genome editing. Cell. 2015;161(3):459-69.
21. Hsu PD, Scott DA, Weinstein JA, Ran FA, Konermann S, Agarwala V, Li Y, Fine EJ, Wu X, Shalem O. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat Biotechnol. 2013;31(9):827-32.
22. Jinek M, Jiang F, Taylor DW, Sternberg SH, Kaya E, Ma E, Anders C, Hauer M, Zhou K, Lin S, Kaplan M, Iavarone AT, Charpentier E, Nogales E, Doudna JA. Structures of Cas9 endonucleases reveal RNA-mediated conformational activation. Science. 2014;343(6176):1247997.
23. Sternberg SH, Redding S, Jinek M, Greene EC, Doudna JA. DNA interrogation by the CRISPR RNA-guided endonuclease Cas9. Nature. 2014;507(7490):62-7.
24. Ranganathan V, Wahlin K, Maruotti J, Zack DJ. Expansion of the CRISPR-Cas9 genome targeting space through the use of H1 promoter-expressed guide RNAs. Nat Commun. 2014;5:4516.
25. Ran FA, Cong L, Yan WX, Scott DA, Gootenberg JS, Kriz AJ, Zetsche B, Shalem O, Wu X, Makarova KS, Koonin EV, Sharp PA, Zhang F. In vivo genome editing using Staphylococcus aureus Cas9. Nature. 2015;520(7546):186-91.
26. Kleinstiver BP, Prew MS, Tsai SQ, Topkar VV, Nguyen NT, Zheng Z, Gonzales APW, Li Z, Peterson RT, Yeh JJ, Aryee MJ, Joung JK. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature. 2015;523(7561):481-5.
27. Esvelt KM, Mali P, Braff JL, Moosburner M, Yaung SJ, Church GM. Orthogonal Cas9 proteins for RNA-guided gene regulation and editing. Nat Methods. 2013;10(11):1116-21.
28. Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. Genome engineering using the CRISPR-Cas9 system. Nat Protoc. 2013;8(11):2281-308.
29. Larson MH, Gilbert LA, Wang X, Lim WA, Weissman JS, Qi LS. CRISPR interference (CRISPRi) for sequence-specific control of gene expression. Nat Protoc. 2013;8(11):2180-96.
30. Perez-Pinera P, Kocak DD, Vockley CM, Adler AF, Kabadi AM, Polstein LR, Thakore PI, Glass KA, Ousterout DG, Leong KW, Guilak F, Crawford GE, Reddy TE, Gersbach CA. RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat Methods. 2013;10(10):973-6.
31. Xie S, Shen B, Zhang C, Huang X, Zhang Y. sgRNAcas9: a software package for designing CRISPR sgRNA and evaluating potential off-target cleavage sites. PLoS One. 2014;9(6):e100448.
32. Cong L, Zhang F. Genome engineering using CRISPR-Cas9 system. Methods Mol Biol. 2015;1239:197-217.
33. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, Zhang F. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013;339(6121):819-23.
34. Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW, Zhang F, Jaenisch R. One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell. 2013;153(4):910-8.
35. Hwang WY, Fu Y, Reyon D, Maeder ML, Tsai SQ, Sander JD, Peterson RT, Yeh JR, Joung JK. Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol. 2013;31(3):227-9.
36. Platt RJ, Chen S, Zhou Y, Yim MJ, Swiech L, Kempton HR, Dahlman JE, Parnas O, Eisenhaure TM, Jovanovic M, Graham DB, Jhunjhunwala S, Heidenreich M, Xavier RJ, Langer R, Anderson DG, Hacohen N, Regev A, Feng G, Sharp PA, Zhang F. CRISPR-Cas9 knockin mice for genome editing and cancer modeling. Cell. 2014;159(2):440-55.
37. Aida T, Chiyo K, Usami T, Ishikubo H, Imahashi R, Wada Y, Tanaka KF, Sakuma T, Yamamoto T, Tanaka K. Cloning-free CRISPR/Cas system facilitates functional cassette knock-in in mice. Genome Biol. 2015;16(1):87.
38. Swiech L, Heidenreich M, Banerjee A, Habib N, Li Y, Trombetta J, Sur M, Zhang F. In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9. Nat Biotechnol. 2015;33(1):102-6.
39. Niu Y, Shen B, Cui Y, Chen Y, Wang J, Wang L, Kang Y, Zhao X, Si W, Li W, Xiang AP, Zhou J, Guo X, Bi Y, Si C, Hu B, Dong G, Wang H, Zhou Z, Li T, Tan T, Pu X, Wang F, Ji S, Zhou Q, Huang X, Ji W, Sha J. Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos. Cell. 2014;156(4):836-43.
40. Incontro S, Asensio CS, Edwards RH, Nicoll RA. Efficient, complete deletion of synaptic proteins using CRISPR. Neuron. 2014;83(5):1051-7.
41. Huang X, Wang Y, Yan W, Smith C, Ye Z, Wang J, Gao Y, Mendelsohn L, Cheng L. Production of gene-corrected adult beta globin protein in human erythrocytes differentiated from patient iPSCs after genome editing of the sickle point mutation. Stem Cells. 2015;33(5):1470-9.
42. Xie F, Ye L, Chang JC, Beyer AI, Wang J, Muench MO, Kan YW. Seamless gene correction of beta-thalassemia mutations in patient-specific iPSCs using CRISPR/Cas9 and piggyBac. Genome Res. 2014;24(9):1526-33.
43. Burt A. Site-specific selfish genes as tools for the control and genetic engineering of natural populations. Proc Biol Sci. 2003;270(1518):921-8.
44. Esvelt KM, Smidler AL, Catteruccia F, Church GM. Concerning RNA-guided gene drives for the alteration of wild populations. Elife. 2014;3:e03401.
45. Li J, Shou J, Guo Y, Tang Y, Wu Y, Jia Z, Zhai Y, Chen Z, Xu Q, Wu Q. Efficient inversions and duplications of mammalian regulatory DNA elements and gene clusters by CRISPR/Cas9. J Mol Cell Biol. 2015;7(4):284-98.
46. Chen WV, Maniatis T. Clustered protocadherins. Development. 2013;140(16):3297-302.
47. Narendra V, Rocha PP, An D, Raviram R, Skok JA, Mazzoni EO, Reinberg D. Transcription. CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation. Science. 2015;347(6225):1017-21.
48. Fanucchi S, Shibayama Y, Burd S, Weinberg MS, Mhlanga MM. Chromosomal contact permits transcription between coregulated genes. Cell. 2013;155(3):606-20.
49. Belmonte JC, Callaway EM, Churchland P, Caddick SJ, Feng G, Homanics GE, Lee KF, Leopold DA, Miller CT, Mitchell JF, Mitalipov S, Moutri AR, Movshon JA, Okano H, Reynolds JH, Ringach D, Sejnowski TJ, Silva AC, Strick PL, Wu J, Zhang F. Brains, genes, and primates. Neuron. 2015;86(3):617-31.
50. Liao J, Karnik R, Gu H, Ziller MJ, Clement K, Tsankov AM, Akopian V, Gifford CA, Donaghey J, Galonska C, Pop R, Reyon D, Tsai SQ, Mallard W, Joung JK, Rinn JL, Gnirke A, Meissner A. Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells. Nat Genet. 2015;47(5):469-78.
51. Tsumura A, Hayakawa T, Kumaki Y, Takebayashi S, Sakaue M, Matsuoka C, Shimotohno K, Ishikawa F, Li E, Ueda HR, Nakayama J, Okano M. Maintenance of self-renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b. Genes Cells. 2006;11(7):805-14.
52. Seipel K, Georgiev O, Schaffner W. Different activation domains stimulate transcription from remote ('enhancer') and proximal ('promoter') positions. EMBO J. 1992;11(13):4961-8.
53. Beerli RR, Segal DJ, Dreier B, Barbas CF 3rd. Toward controlling gene expression at will: specific regulation of the erbB-2/HER-2 promoter by using polydactyl zinc finger proteins constructed from modular building blocks. Proc Natl Acad Sci USA. 1998;95(25):14628-33.
54. Gao X, Tsang JC, Gaba F, Wu D, Lu L, Liu P. Comparison of TALE designer transcription factors and the CRISPR/dCas9 in regulation of gene expression by targeting enhancers. Nucleic Acids Res. 2014;42(20):e155.
55. Margolin JF, Friedman JR, Meyer WK, Vissing H, Thiesen HJ, Thiesen FJ 3rd. Kruppel-associated boxes are potent transcriptional repression domains. Proc Natl Acad Sci USA. 1994;91(10):4509-13.
56. Ayer DE, Laherty CD, Lawrence QA, Armstrong AP, Eisenman RN. Mad proteins contain a dominant transcription repression domain. Mol Cell Biol. 1996;16(10):5772-81.
57. Konermann S, Brigham MD, Trevino AE, Hsu PD, Heidenreich M, Cong L, Platt RJ, Scott DA, Church GM, Zhang F. Optical control of mammalian endogenous transcription and epigenetic states. Nature. 2013;500(7463):472-6.
58. Kearns NA, Pham H, Tabak B, Genga RM, Silverstein NJ, Garber M, Maehr R. Functional annotation of native enhancers with a Cas9-histone demethylase fusion. Nat Methods. 2015;12(5):401-3.
59. Ma AN, Wang H, Guo R, Wang YX, Li W, Cui J, Wang G, Hoffman AR, Hu JF. Targeted gene suppression by inducing de novo DNA methylation in the gene promoter. Epigenetics Chromatin. 2014;7:20.
60. Grimmer MR, Stolzenburg S, Ford E, Lister R, Blancafort P, Farnham PJ. Analysis of an artificial zinc finger epigenetic modulator: widespread binding but limited regulation. Nucleic Acids Res. 2014;42(16):10856-68.
61. Snowden AW, Gregory PD, Case CC, Pabo CO. Gene-specific targeting of H3K9 methylation is sufficient for initiating repression in vivo. Curr Biol. 2002;12(24):2159-66.
62. Falahi F, Huisman C, Kazemier HG, van der Viles P, Kok K, Hospers GAP, Rots MG. Towards sustained silencing of HER2/neu in cancer by epigenetic editing. Mol Cancer Res. 2013;11(9):1029-39.
63. Li F, Papworth M, Minczuk M, Rohde C, Zhang Y, Ragozin S, Jeltsch A. Chimeric DNA methyltransferases target DNA methylation to specific DNA sequences and repress expression of target genes. Nucleic Acids Res. 2007;35(1):100-12.
64. Meister GE, Chandrasegaran S, Ostermeier M. Heterodimeric DNA methyltransferases as a platform for creating designer zinc finger methyltransferases for targeted DNA methylation in cells. Nucleic Acids Res. 2010;38(5):1749-59.
65. Rivenbark AG, Stolzenburg S, Beltran AS, Yuan X, Rots MG, Strahl BD, Blancafort P. Epigenetic reprogramming of cancer cells via targeted DNA methylation. Epigenetics. 2012;7(4):350-60.
66. Chaikind B, Kilambi KP, Gray JJ, Ostermeier M. Targeted DNA methylation using an artificially bisected M. HhaI fused to zinc fingers. PLoS One. 2012;7(9):e44852.
67. Siddique AN, Nunna S, Rajavelu A, Zhang Y, Jurkowska RZ, Reinhardt R, Rots MG, Ragozin S, Jurkowski TP, Jeltsch A. Targeted methylation and gene silencing of VEGF-A in human cells by using a designed Dnmt3a-Dnmt3L single-chain fusion protein with increased DNA methylation activity. J Mol Biol. 2013;425(3):479-91.
68. Nunna S, Reinhardt R, Ragozin S, Jeltsch A. Targeted methylation of the epithelial cell adhesion molecule (EpCAM) promoter to silence its expression in ovarian cancer cells. PLoS One. 2014;9(1):e87703.
69. Chaikind B, Ostermeier M. Directed evolution of improved zinc finger methyltransferases. PLoS One. 2014;9(5):e96931.
70. Stolzenburg S, Beltran AS, Swift-Scanlan T, Rivenbark AG, Rashwan R, Blancafort P. Stable oncogenic silencing in vivo by programmable and targeted de novo DNA methylation in breast cancer. Oncogene. 2015. doi: 10.1038/onc.2014.470.
71. Kungulovski G, Nunna S, Thomas M, Zanger UM, Reinhardt R, Jeltsch A. Targeted epigenome editing of an endogenous locus with chromatin modifiers is not stably maintained. Epigenetics Chromatin. 2015;8:12.
72. Gregory DJ, Zhang Y, Kobzik L, Fedulov AV. Specific transcriptional enhancement of inducible nitric oxide synthase by targeted promoter demethylation. Epigenetics. 2013;8(11):1205-12.
73. Maeder ML, Linder SJ, Reyon D, Angstman JF, Fu Y, Sander JD, Joung JK. Robust, synergistic regulation of human gene expression using TALE activators. Nat Methods. 2013;10(3):243-5.
74. Cho H, Kang JG, Lee J, Lee J, Jeon SK, Ko J, Kim D, Park K, Kim Y, Kim N. Direct regulation of E-cadherin by targeted histone methylation of TALE-SET fusion protein in cancer cells. Oncotarget. 2015 [Epub ahead of print].
75. Mendenhall EM, Williamson KE, Reyon D, Zou JY, Ram O, Joung JK, Bernstein BE. Locus-specific editing of histone modifications at endogenous enhancers. Nat Biotechnol. 2013;31(12):1133-6.
76. Bernstein DL, Le Lay JE, Ruano EG, Kaestner KH. TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts. J Clin Invest. 2015;125(5):1998-2006.
77. Maeder ML, Angstman JF, Richardson ME, Linder SJ, Cascio VM, Tsai SQ, Ho QH, Sander JD, Reyon D, Bernstein BE, Costello JF, Wilkinson MF, Joung JK. Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins. Nat Biotechnol. 2013;31(12):1137-42.
78. Chen H, Kazemier HG, de Groote ML, Ruiters MH, Xu GL, Rots MG. Induced DNA demethylation by targeting Ten-Eleven Translocation 2 to the human ICAM-1 promoter. Nucleic Acids Res. 2014;42(3):1563-74.
79. Maeder ML, Linder SJ, Cascio VM, Fu Y, Ho QH, Joung JK. CRISPR RNA-guided activation of endogenous human genes. Nat Methods. 2013;10(10):977-9.
80. Cheng AW, Wang H, Yang H, Shi L, Katz Y, Theunissen TW, Rangarajan S, Shivalila CS, Dadon DB, Jaenisch R. Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system. Cell Res. 2013;23(10):1163-71.
81. Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA, Torres SE, Stern-Ginossar N, Brandman O, Whitehead EH, Doudna JA, Lim WA, Weissman JS, Qi LS. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell. 2013;154(2):442-51.
82. Qi LS, Larson MH, Gilbert LA, Doudna JA, Weissman JS, Arkin AP, Lim WA. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell. 2013;152(5):1173-83.
83. Mali P, Aach J, Stranges PB, Esvelt KM, Moosburner M, Kosuri S, Yang L, Church GM. CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat Biotechnol. 2013;31(9):833-8.
84. Konermann S, Brigham MD, Trevino AE, Joung J, Abudayyeh OO, Barcena C, Hsu PD, Habib N, Gootenberg JS, Nishimasu H, Nureki O, Zhang F. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature. 2015;517(7536):583-8.
85. Kearns NA, Genga RM, Enuameh MS, Garber M, Wolfe SA, Maehr R. Cas9 effector-mediated regulation of transcription and differentiation in human pluripotent stem cells. Development. 2014;141(1):219-23.
86. Sander JD, Joung JK. CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol. 2014;32(4):347-55.
87. Gilbert LA, Horlbeck MA, Adamson B, Villalta JE, Chen Y, Whitehead EH, Guimaraes C, Panning B, Ploegh HL, Bassik MC, Qi LS, Kampmann M, Weissman JS. Genome-scale CRISPR-mediated control of gene repression and activation. Cell. 2014;159(3):647-61.
88. Zalatan JG, Lee ME, Almeida R, Gilbert LA, Whitehead EH, La Russa M, Tsai JC, Weissman JS, Dueber JE, Qi LS, Lim WA. Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds. Cell. 2015;160(1-2):339-50.
89. Telese F, Ma Q, Perez P, Notani D, Oh S, Li W, Comoletti D, Ohgi K, Taylor H, Rosenfeld M. LRP8-Reelin-regulated neuronal enhancer signature underlying learning and memory formation. Neuron. 2015;86(3):696-710.
90. Chakraborty S, Ji H, Kabadi AM, Gersbach CA, Christoforou N, Leong KW. A CRISPR/Cas9-based system for reprogramming cell lineage specification. Stem Cell Rep. 2014;3(6):940-7.
91. Hilton IB, D'Ippolito AM, Vockley CM, Thakore PI, Crawford GE, Reddy TE, Gersbach CA. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nat Biotech. 2015;33(5):510-7.
92. Carroll D. Staying on target with CRISPR-Cas. Nat Biotechnol. 2013;31(9):807-9.
93. Hendel A, Fine EJ, Bao G, Porteus MH. Quantifying on- and off-target genome editing. Trends Biotechnol. 2015;33(2):132-40.
94. Wei C, Liu J, Yu Z, Zhang B, Gao G, Jiao R. TALEN or Cas9 - rapid, efficient and specific choices for genome modifications. J Genet Genom. 2013;40(6):281-9.
95. Hu J, Lei Y, Wong WK, Liu S, Lee KC, He X, You W, Zhou R, Guo JT, Chen X, Peng X, Sun H, Huang H, Zhao H, Feng B. Direct activation of human and mouse Oct4 genes using engineered TALE and Cas9 transcription factors. Nucleic Acids Res. 2014;42(7):4375-90.
96. Tanenbaum ME, Gilbert LA, Qi LS, Weissman JS, Vale RD. A protein-tagging system for signal amplification in gene expression and fluorescence imaging. Cell. 2014;159(3):635-46.
97. Chavez A, Scheiman J, Vora S, Pruitt BW, Tuttle M, P R Iyer E, Lin S, Kiani S, Guzman CD, Wiegand DJ, Ter-Ovanesyan D, Braff JL, Davidsohn N, Housden BE, Perrimon N, Weiss R, Aach J, Collins JJ, Church GM. Highly efficient Cas9-mediated transcriptional programming. Nat Methods. 2015;12(4):326-8.
98. Shechner DM, Hacisuleyman E, Younger ST, Rinn JL. Multiplexable, locus-specific targeting of long RNAs with CRISPR-Display. Nat Methods. 2015;12(7):664-70.
99. Liu H, Yu X, Li K, Klejnot J, Yang H, Lisiero D, Lin C. Photoexcited CRY2 interacts with CIB1 to regulate transcription and floral initiation in Arabidopsis. Science. 2008;322(5907):1535-9.
100. Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K. Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci. 2005;8(9):1263-8.
101. Adamantidis AR, Tsai HC, Boutrel B, Zhang F, Stuber GD, Budygin EA, Tourino C, Bonci A, Deisseroth K, de Lecea L. Optogenetic interrogation of dopaminergic modulation of the multiple phases of reward-seeking behavior. J Neurosci. 2011;31(30):10829-35.
102. Nihongaki Y, Yamamoto S, Kawano F, Suzuki H, Sato M. CRISPR-Cas9-based photoactivatable transcription system. Chem Biol. 2015;22(2):169-74.
103. Polstein LR, Gersbach CA. A light-inducible CRISPR-Cas9 system for control of endogenous gene activation. Nat Chem Biol. 2015;11(3):198-200.
104. Mercer AC, Gaj T, Sirk SJ, Lamb BM, Barbas CF 3rd. Regulation of endogenous human gene expression by ligand-inducible TALE transcription factors. ACS Synth Biol. 2014;3(10):723-30.
105. Chen B, Gilbert LA, Cimini BA, Schnitzbauer J, Zhang W, Li GW, Park J, Blackburn EH, Weissman JS, Qi LS, Huang B. Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell. 2013;155(7):1479-91.
106. 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. 2014;5(2):163-72.
107. Pederson T. Repeated TALEs: visualizing DNA sequence localization and chromosome dynamics in live cells. Nucleus. 2014;5(1):28-31.
108. Ma H, Naseri A, Reyes-Gutierrez P, Wolfe SA, Zhang S, Pederson T. Multicolor CRISPR labeling of chromosomal loci in human cells. Proc Natl Acad Sci USA. 2015;112(10):3002-7.
109. Byrum SD, Raman A, Taverna SD, Tackett AJ. ChAP-MS: a method for identification of proteins and histone posttranslational modifications at a single genomic locus. Cell Rep. 2012;2(1):198-205.
110. Fujita T, Asano Y, Ohtsuka J, Takada Y, Saito K, Ohki R, Fujii H. Identification of telomere-associated molecules by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP). Sci Rep. 2013;3:3171.
111. Fujita T, Fujii H. Efficient isolation of specific genomic regions and identification of associated proteins by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using CRISPR. Biochem Biophys Res Commun. 2013;439(1):132-6.
112. Waldrip ZJ, Byrum SD, Storey AJ, Gao J, Byrd AK, Mackintosh SG, Wahls WP, Taverna SD, Raney KD, Tackett AJ. A CRISPR-based approach for proteomic analysis of a single genomic locus. Epigenetics. 2014;9(9):1207-11.
113. Byrum SD, Taverna SD, Tackett AJ. Purification of a specific native genomic locus for proteomic analysis. Nucleic Acids Res. 2013;41(20):e195.
114. Li L, He Z, Wei X, Gao G, Wei Y. Challenges in CRISPR/CAS9 delivery: potential roles of non-viral vectors. Hum Gene Ther. 2015;26(7):452-62.
115. Gori JL, Hsu PD, Maeder ML, Shen S, Welstead GG, Bumcrot D. Delivery and specificity of CRISPR-Cas9 genome editing technologies for human gene therapy. Hum Gene Ther. 2015;26(7):443-51.
116. Liu DR. Delivery of negatively charged proteins using cationic lipids. 2015 (20150118216).
117. Wang D, Mou H, Li S, Li Y, Hough S, Tran K, Li J, Yin H, Anderson DG, Sontheimer E. Adenovirus-mediated somatic genome editing of Pten by CRISPR/Cas9 in mouse liver in spite of Cas9-specific immune responses. Hum Gene Ther. 2015;26(7):432-42.
118. Cox DB, Platt RJ, Zhang F. Therapeutic genome editing: prospects and challenges. Nat Med. 2015;21(2):121-31.
119. Gaj T, Guo J, Kato Y, Sirk SJ, Barbas CF 3rd. Targeted gene knockout by direct delivery of zinc-finger nuclease proteins. Nat Methods. 2012;9(8):805-7.
120. Gaj T, Liu J, Anderson KE, Sirk SJ, Barbas CF 3rd. Protein delivery using Cys2-His2 zinc-finger domains. ACS Chem Biol. 2014;9(8):1662-7.
121. Liu J, Gaj T, Wallen MC, Barbas CF 3rd. Improved cell-penetrating zinc-finger nuclease proteins for precision genome engineering. Mol Ther Nucleic Acids. 2015;4:e232.
122. Liu J, Gaj T, Patterson JT, Sirk SJ, Barbas CF 3rd. Cell-penetrating peptide-mediated delivery of TALEN proteins via bioconjugation for genome engineering. PLoS One. 2014;9(1):e85755.
123. Zuris JA, Thompson DB, Shu Y, Guilinger JP, Bessen JL, Hu JH, Maeder ML, Joung JK, Chen ZY, Liu DR. Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo. Nat Biotechnol. 2015;33(1):73-80.
124. Schumann K, Lin S, Boyer E, Simeonov DR, Subramaniam M, Gate RE, Haliburton GE, Ye CJ, Bluestone JA, Doudna JA, Marson A. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins. Proc Natl Acad Sci. 2015;12(33):10437-42.
125. Heller EA, Cates HM, Pena CJ, Sun H, Shao N, Feng J, Golden SA, Herman JP, Walsh JJ, Mazei-Robison M, Ferguson D, Knight S, Gerber MA, Nievera C, Han MH, Russo SJ, Tamminga CS, Neve RL, Shen L, Zhang HS, Zhang F, Nestler EJ. Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors. Nat Neurosci. 2014;17(12):1720-7.