

40. Fonfara, I.
et al.
(2016) The CRISPR-associated DNA-cleaving
enzyme Cpf1 also processes precursor CRISPR RNA.
Nature
532, 517
–
521
41. Abudayyeh, O.O.
et al.
(2016) C2c2 is a single-component
programmable RNA-guided RNA-targeting CRISPR effector.
Science
353, aaf5573
42. Ran, F.A.
et al.
(2013) Double nicking by RNA-guided CRISPR
Cas9 for enhanced genome editing speci
fi
city.
Cell
154, 1380
–
1389
43. Komor, A.C.
et al.
(2016) Programmable editing of a target base
in genomic DNA without double-stranded DNA cleavage.
Nature
533, 420
–
424
44. Qi, L.S.
et al.
(2013) Repurposing CRISPR as an RNA-guided
platform for sequence-speci
fi
c control of gene expression.
Cell
152, 1173
–
1183
45. Peters, J.M.
et al.
(2016) A comprehensive, CRISPR-based
functional analysis of essential genes in bacteria.
Cell
165,
1493
–
1506
46. Gilbert, L.A.
et al.
(2013) CRISPR-mediated modular RNA-
guided regulation of transcription in eukaryotes.
Cell
154,
442
–
451
47. Gilbert, L.A.
et al.
(2014) Genome-scale CRISPR-mediated
control
of gene repression and activation.
Cell
159,
647
–
661
48. Konermann, S.
et al.
(2015) Genome-scale transcriptional acti-
vation by an engineered CRISPR-Cas9 complex.
Nature
517,
583
–
588
49. Larson, M.H.
et al.
(2013) CRISPR interference (CRISPRi) for
sequence-speci
fi
c control of gene expression.
Nat. Protoc.
8,
2180
–
2196
50. Zhao, Y.
et al.
(2014) Sequence-speci
fi
c inhibition of microRNA
via CRISPR/CRISPRi system.
Sci. Rep.
4, 3943
51. Perez-Pinera, P.
et al.
(2013) RNA-guided gene activation by
CRISPR-Cas9-based transcription factors.
Nat. Methods
10,
973
–
976
52. Cheng, A.W.
et al.
(2013) Multiplexed activation of endogenous
genes by CRISPR-on, an RNA-guided transcriptional activator
system.
Cell Res.
23, 1163
–
1171
53. Tanenbaum, M.E.
et al.
(2014) A protein-tagging system for
signal ampli
fi
cation in gene expression and
fl
uorescence imag-
ing.
Cell
159, 635
–
646
54. Chavez, A.
et al.
(2015) Highly ef
fi
cient Cas9-mediated transcrip-
tional programming.
Nat. Methods
12, 326
–
328
55. Chavez, A.
et al.
(2016) Comparison of Cas9 activators in multiple
species.
Nat. Methods
13, 563
–
567
56. Zalatan, J.G.
et al.
(2015) Engineering complex synthetic tran-
scriptional programs with CRISPR RNA scaffolds.
Cell
160, 339
–
350
57. Hilton, I.B.
et al.
(2015) Epigenome editing by a CRISPR-Cas9-
based acetyltransferase activates genes from promoters and
enhancers.
Nat. Biotechnol.
33, 510
–
517
58. Kearns, N.A.
et al.
(2015) Functional annotation of native
enhancers with a Cas9-histone demethylase fusion.
Nat. Meth-
ods
12, 401
–
403
59. Thakore, P.I.
et al.
(2015) Highly speci
fi
c epigenome editing by
CRISPR-Cas9 repressors for silencing of distal regulatory ele-
ments.
Nat. Methods
12, 1143
–
1149
60. Vojta, A.
et al.
(2016) Repurposing the CRISPR-Cas9 system
for targeted DNA methylation.
Nucleic. Acids Res.
44, 5615
–
5628
61. Kearns, N.A.
et al.
(2014) Cas9 effector-mediated regulation of
transcription and differentiation in human pluripotent stem cells.
Development
141, 219
–
223
62. Shi, J.
et al.
(2015) Discovery of cancer drug targets by CRISPR-
Cas9 screening of protein domains.
Nat. Biotechnol.
33, 661
–
667
63. Korkmaz, G.
et al.
(2016) Functional genetic screens for
enhancer elements in the human genome using CRISPR-
Cas9.
Nat. Biotechnol.
34, 192
–
198
64. Shalem, O.
et al.
(2014) Genome-scale CRISPR-Cas9 knockout
screening in human cells.
Science
343, 84
–
87
65. Bernstein, B.E.
et al.
(2006) A bivalent chromatin structure marks
key developmental genes in embryonic stem cells.
Cell
125, 315
–
326
66. Zhou, Y.
et al.
(2014) High-throughput screening of a CRISPR/
Cas9 library for functional genomics in human cells.
Nature
509,
487
–
491
67. Chen, S.
et al.
(2015) Genome-wide CRISPR screen in a mouse
model of tumor growth and metastasis.
Cell
160, 1246
–
1260
68. Parnas, O.
et al.
(2015) A genome-wide CRISPR screen in
primary immune cells to dissect regulatory networks.
Cell
162,
675
–
686
69. Wong, A.S.
et al.
(2016) Multiplexed barcoded CRISPR-Cas9
screening enabled by CombiGEM.
Proc. Natl. Acad. Sci. U.S.A.
113, 2544
–
2549
70. Evers, B.
et al.
(2016) CRISPR knockout screening outperforms
shRNA and CRISPRi in identifying essential genes.
Nat. Biotech-
nol.
34, 631
–
633
71. Morgens, D.W.
et al.
(2016) Systematic comparison of CRISPR/
Cas9 and RNAi screens for essential genes.
Nat. Biotechnol.
34,
634
–
636
72. Lane, A.B.
et al.
(2015) Enzymatically generated CRISPR libraries
for genome labeling and screening.
Dev Cell
34, 373
–
378
73. Friedland, A.E.
et al.
(2013) Heritable genome editing in
C.
elegans
via a CRISPR-Cas9 system.
Nat. Methods
10, 741
–
743
74. Bassett, A.R.
et al.
(2013) Highly ef
fi
cient targeted mutagenesis
of
Drosophila
with the CRISPR/Cas9 system.
Cell Rep.
4, 220
–
228
75. Jao, L.E.
et al.
(2013) Ef
fi
cient multiplex biallelic zebra
fi
sh genome
editing using a CRISPR nuclease system.
Proc. Natl. Acad. Sci.
U.S.A.
110, 13904
–
13909
76. Chang, N.
et al.
(2013) Genome editing with RNA-guided Cas9
nuclease in zebra
fi
sh embryos.
Cell Res.
23, 465
–
472
77. Li, W.
et al.
(2013) Simultaneous generation and germline trans-
mission of multiple gene mutations in rat using CRISPR-Cas
systems.
Nat. Biotechnol.
31, 684
–
686
78. Lv, Q.
et al.
(2016) Ef
fi
cient generation of myostatin gene mutated
rabbit by CRISPR/Cas9.
Sci. Rep.
6, 25029
79. Yan, Q.
et al.
(2014) Generation of multi-gene knockout rabbits
using the Cas9/gRNA system.
Cell Regen. (Lond).
3, 12
80. Wang, X.
et al.
(2015) Generation of gene-modi
fi
ed goats target-
ing MSTN and FGF5 via zygote injection of CRISPR/Cas9 sys-
tem.
Sci. Rep.
5, 13878
81. Crispo, M.
et al.
(2015) Ef
fi
cient generation of myostatin knock-
out sheep using CRISPR/Cas9 technology and microinjection
into zygotes.
PLoS ONE
10, e0136690
82. Zou, Q.
et al.
(2015) Generation of gene-target dogs using
CRISPR/Cas9 system.
J. Mol. Cell Biol.
7, 580
–
583
83. Wang, K.
et al.
(2015) Ef
fi
cient generation of myostatin mutations
in pigs using the CRISPR/Cas9 System.
Sci. Rep.
5, 16623
84. Niu, Y.
et al.
(2014) Generation of gene-modi
fi
ed cynomolgus
monkey via Cas9/RNA-mediated gene targeting in one-cell
embryos.
Cell
156, 836
–
843
85. Wang, H.
et al.
(2013) One-step generation of mice carrying
mutations in multiple genes by CRISPR/Cas-mediated genome
engineering.
Cell
153, 910
–
918
86. Yang, H.
et al.
(2013) One-step generation of mice carrying
reporter and conditional alleles by CRISPR/Cas-mediated
genome engineering.
Cell
154, 1370
–
1379
87. Platt, R.J.
et al.
(2014) CRISPR-Cas9 knockin mice for genome
editing and cancer modeling.
Cell
159, 440
–
455
88. Chiou, S.H.
et al.
(2015) Pancreatic cancer modeling using
retrograde viral vector delivery and in vivo CRISPR/Cas9-medi-
ated somatic genome editing.
Genes. Dev.
29, 1576
–
1585
89. Swiech, L.
et al.
(2015) In vivo interrogation of gene function in the
mammalian brain using CRISPR-Cas9.
Nat. Biotechnol.
33, 102
–
106
90. Sanchez-Rivera, F.J.
et al.
(2014) Rapid modelling of cooperating
genetic events in cancer through somatic genome editing.
Nature
516, 428
–
431
91. Xue, W.
et al.
(2014) CRISPR-mediated direct mutation of cancer
genes in the mouse liver.
Nature
514, 380
–
384
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