Enhanced rice blast resistance by CRISPR/ Cas9-Targeted mutagenesis of the ERF transcription factor gene OsERF922

PLoS ONE

Volumn 11, Issue 4, 2016, Pages

  Wang, Fujun ^a,b   Wang, Chunlian ^b   Liu, Piqing ^a   Lei, Cailin ^b   Hao, Wei ^b   Gao, Ying ^b   Liu, Yao Guang ^c   Zhao, Kaijun ^b  

^a GUANGXI UNIVERSITY   (China)

^b INSTITUTE OF PLANT PROTECTION   (China)

^c SOUTH CHINA AGRICULTURAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

CRISPR ASSOCIATED PROTEIN; ETHYLENE RESPONSIVE FACTOR; NUCLEASE; SEQUENCE SPECIFIC NUCLEASE; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR ERF; UNCLASSIFIED DRUG;

AGROBACTERIUM TUMEFACIENS; AGRONOMIC TRAIT; ARTICLE; DNA MODIFICATION; DOUBLE STRANDED DNA BREAK; ELECTROPORATION; EXPRESSION VECTOR; GENE SEGREGATION; GENE STRUCTURE; GENETIC ENGINEERING AND GENE TECHNOLOGY; GENETIC TRANSFORMATION; HOMOZYGOSITY; HOST RESISTANCE; JAPONICA RICE; MUTAGENESIS; NONHUMAN; PLANT GENETICS; PLANT GROWTH; PLANT HEIGHT; PLANT STRESS; PROTOPLAST; RICE BLAST; RNA EDITING; RNA INTERFERENCE; SEED WEIGHT; TRANSGENIC PLANT; CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEAT; GENETICS; MICROBIOLOGY; NUCLEOTIDE SEQUENCE; ORYZA; PLANT DISEASE; PLANT GENE; SEQUENCE HOMOLOGY;

BASE SEQUENCE; CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEATS; GENES, PLANT; MUTAGENESIS; ORYZA; PLANT DISEASES; PLANTS, GENETICALLY MODIFIED; SEQUENCE HOMOLOGY, NUCLEIC ACID; TRANSCRIPTION FACTORS;

EID: 84977500985     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0154027     Document Type: Article

References (83)

1. Dean R, Van Kan JA, Pretorius ZA, Hammond-Kosack KE, Di Pietro A, Spanu PD, et al. The Top 10 fungal pathogens in molecular plant pathology. Mol Plant Pathol. 2012; 13(4): 414-430. doi: 10.1111/j. 1364-3703.2011.00783.x PMID: 22471698
2. Liu W, Liu J, Triplett L, Leach JE, Wang GL. Novel insights into rice innate immunity against bacterial and fungal pathogens. Annu Rev Phytopathol. 2014; 52: 213-241. doi: 10.1146/annurev-phyto-102313-045926 PMID: 24906128
3. Boyd LA, Ridout C, O'Sullivan DM, Leach JE, Leung H. Plant-pathogen interactions: disease resistance in modern agriculture. Trends Genet. 2013; 29(4): 233-240. doi: 10.1016/j.tig.2012.10.011 PMID: 23153595
4. Miah G, Rafii MY, Ismail MR, Puteh AB, Rahim HA, Asfaliza R, et al. Blast resistance in rice: a review of conventional breeding to molecular approaches. Mol Biol Rep. 2013; 40(3): 2369-2388. doi: 10.1007/ s11033-012-2318-0 PMID: 23184051
5. Postel S, Kemmerling B. Plant systems for recognition of pathogen-associated molecular patterns. Semin Cell Dev Biol. 2009; 20(9): 1025-1031. doi: 10.1016/j.semcdb.2009.06.002 PMID: 19540353
6. Jones JD, Dangl JL. The plant immune system. Nature. 2006; 444(7117): 323-329. PMID: 17108957
7. Chisholm ST, Coaker G, Day B, Staskawicz BJ. Host-microbe interactions: shaping the evolution of the plant immune response. Cell. 2006; 124(4): 803-814. PMID: 16497589
8. Rojo E, Solano R, Sánchez-Serrano JJ. Interactions between signaling compounds involved in plant defense. J Plant Growth Regul. 2003; 22(1): 82-98.
9. Glazebrook J. Contrasting mechanisms of defense against biotrophic and necrotrophic pathogens. Annu Rev Phytopathol. 2005; 43: 205-227. PMID: 16078883
10. De Vos M, Van Oosten VR, Van Poecke RM, Van Pelt JA, Pozo MJ, Mueller MJ, et al. Signal signature and transcriptome changes of Arabidopsis during pathogen and insect attack. Mol Plant-Microbe Interact. 2005; 18(9): 923-937. PMID: 16167763
11. Jung J, Won SY, Suh SC, Kim H, Wing R, Jeong Y, et al. The barley ERF-type transcription factor HvRAF confers enhanced pathogen resistance and salt tolerance in Arabidopsis. Planta. 2007; 225 (3): 575-588. PMID: 16937017
12. Vogel MO, Moore M, Konig K, Pecher P, Alsharafa K, Lee J, et al. Fast retrograde signaling in response to high light involves metabolite export, MITOGEN-ACTIVATED PROTEIN KINASE6, and AP2/ERF transcription factors in Arabidopsis. Plant cell. 2014; 26(3): 1151-1165. doi: 10.1105/tpc.113.121061 PMID: 24668746
13. Muller M, Munne-Bosch S. Ethylene response factors: a key regulatory hub in hormone and stress signaling. Plant Physiol. 2015; 169(1): 32-41. doi: 10.1104/pp.15.00677 PMID: 26103991
14. Cao Y, Song F, Goodman RM, Zheng Z. Molecular characterization of four rice genes encoding ethylene-responsive transcriptional factors and their expressions in response to biotic and abiotic stress. J Plant Physiol. 2006; 163(11): 1167-1178. PMID: 16436304
15. Lai Y, Dang F, Lin J, Yu L, Shi Y, Xiao Y, et al. Overexpression of a Chinese cabbage BrERF11 transcription factor enhances disease resistance to Ralstonia solanacearum in tobacco. Plant Physiol Biochem. 2013; 62: 70-78. doi: 10.1016/j.plaphy.2012.10.010 PMID: 23201563
16. Sherif S, El-Sharkawy I, Paliyath G, Jayasankar S. PpERF3b, a transcriptional repressor from peach, contributes to disease susceptibility and side branching in EAR-dependent and -independent fashions. Plant Cell Rep. 2013; 32(7): 1111-1124. doi: 10.1007/s00299-013-1405-6 PMID: 23515898
17. Tian Z, He Q, Wang H, Liu Y, Zhang Y, Shao F, et al. The potato ERF transcription factor StERF3 negatively regulates resistance to Phytophthora infestans and salt tolerance in potato. Plant cell Physiol. 2015; 56(5): 992-1005. doi: 10.1093/pcp/pcv025 PMID: 25681825
18. Liu DF, Chen XJ, Liu JQ, Ye JC, Guo ZJ. The rice ERF transcription factor OsERF922 negatively regulates resistance to Magnaporthe oryzae and salt tolerance. J Exp Bot. 2012; 63(10): 3899-3912. doi: 10.1093/jxb/ers079 PMID: 22442415
19. Jia Y. Marker assisted selection for the control of rice blast disease. Pestic Outlook. 2003; 14(4): 150-152.
20. Wang H, Hao J, Chen X, Hao Z, Wang X, Lou Y, et al. Overexpression of rice WRKY89 enhances ultraviolet B tolerance and disease resistance in rice plants. Plant Mol Biol. 2007; 65(6): 799-815. PMID: 17960484
21. Chen X, Guo Z. Tobacco OPBP1 enhances salt tolerance and disease resistance of transgenic rice. Int J Mol Sci. 2008; 9(12): 2601-2613. doi: 10.3390/ijms9122601 PMID: 19330095
22. Bundo M, Coca M. Enhancing blast disease resistance by overexpression of the calcium-dependent protein kinase OsCPK4 in rice. Plant Biotechnol J. 2015 Nov 18. doi: 10.1111/pbi.12500
23. Jiang CJ, Shimono M, Maeda S, Inoue H, Mori M, Hasegawa M, et al. Suppression of the rice fatty-acid desaturase gene OsSSI2 enhances resistance to blast and leaf blight diseases in rice. Mol Plant-Microbe Interact. 2009; 22(7): 820-829. doi: 10.1094/MPMI-22-7-0820 PMID: 19522564
24. Yara A, Yaeno T, Hasegawa M, Seto H, Montillet JL, Kusumi K, et al. Disease resistance against Magnaporthe grisea is enhanced in transgenic rice with suppression of omega-3 fatty acid desaturases. Plant Cell Physiol. 2007; 48(9): 1263-1274. PMID: 17716996
25. Yara A, Yaeno T, Hasegawa M, Seto H, Seo S, Kusumi K, et al. Resistance to Magnaporthe grisea in transgenic rice with suppressed expression of genes encoding allene oxide cyclase and phytodienoic acid reductase. Biochem Biophys Res Commun. 2008; 376(3): 460-465. doi: 10.1016/j.bbrc.2008.08. 157 PMID: 18786507
26. McGinnis KM. RNAi for functional genomics in plants. Brief Funct Genomics. 2010; 9(2): 111-117. doi: 10.1093/bfgp/elp052 PMID: 20053816
27. Baltes NJ, Voytas DF. Enabling plant synthetic biology through genome engineering. Trends Biotechnol. 2015; 33(2): 120-131. doi: 10.1016/j.tibtech.2014.11.008 PMID: 25496918
28. Weeks DP, Spalding MH, Yang B. Use of designer nucleases for targeted gene and genome editing in plants. Plant Biotechnol J. 2016; 14(2): 483-495. doi: 10.1111/pbi.12448 PMID: 26261084
29. Feng Z, Zhang B, Ding W, Liu X, Yang DL, Wei P, et al. Efficient genome editing in plants using a CRISPR/Cas system. Cell Res. 2013; 23(10): 1229-1232. doi: 10.1038/cr.2013.114 PMID: 23958582
30. Jiang W, Zhou H, Bi H, Fromm M, Yang B, Weeks DP. Demonstration of CRISPR/Cas9/sgRNA-mediated targeted gene modification in Arabidopsis, tobacco, sorghum and rice. Nucleic Acids Res. 2013; 41(20): e188. doi: 10.1093/nar/gkt780 PMID: 23999092
31. Miao J, Guo D, Zhang J, Huang Q, Qin G, Zhang X, et al. Targeted mutagenesis in rice using CRISPR-Cas system. Cell Res. 2013; 23(10): 1233-1236. doi: 10.1038/cr.2013.123 PMID: 23999856
32. Shan Q, Wang Y, Li J, Zhang Y, Chen K, Liang Z, et al. Targeted genome modification of crop plants using a CRISPR-Cas system. Nat Biotech. 2013; 31(8): 686-688.
33. Xu R, Li H, Qin R, Wang L, Li L, Wei P, et al. Gene targeting using the Agrobacterium tumefaciensmediated CRISPR-Cas system in rice. Rice. 2014; 7(1): 5. doi: 10.1186/s12284-014-0005-6 PMID: 24920971
34. Xu RF, Li H, Qin RY, Li J, Qiu CH, Yang YC, et al. Generation of inheritable and "transgene clean" targeted genome-modified rice in later generations using the CRISPR/Cas9 system. Sci Rep. 2015; 5: 11491. doi: 10.1038/srep11491 PMID: 26089199
35. Zhang H, Zhang J, Wei P, Zhang B, Gou F, Feng Z, et al. The CRISPR/Cas9 system produces specific and homozygous targeted gene editing in rice in one generation. Plant Biotechnol J. 2014; 12(6): 797-807. doi: 10.1111/pbi.12200 PMID: 24854982
36. Zhou H, Liu B, Weeks DP, Spalding MH, Yang B. Large chromosomal deletions and heritable small genetic changes induced by CRISPR/Cas9 in rice. Nucleic Acids Res. 2014; 42(17): 10903-10914. doi: 10.1093/nar/gku806 PMID: 25200087
37. Endo M, Mikami M, Toki S. Multigene knockout utilizing off-target mutations of the CRISPR/Cas9 system in rice. Plant Cell Physiol. 2015; 56(1): 41-47. doi: 10.1093/pcp/pcu154 PMID: 25392068
38. Ma X, Zhang Q, Zhu Q, Liu W, Chen Y, Qiu R, et al. A robust CRISPR/Cas9 system for convenient, high-efficiency multiplex genome editing in monocot and dicot plants. Mol Plant. 2015; 8(8): 1274-1284. doi: 10.1016/j.molp.2015.04.007 PMID: 25917172
39. Shan Q, Wang Y, Li J, Gao C. Genome editing in rice and wheat using the CRISPR/Cas system. Nat Protoc. 2014; 9(10): 2395-2410. doi: 10.1038/nprot.2014.157 PMID: 25232936
40. Wang C, Shen L, Fu Y, Yan C, Wang K. A simple CRISPR/Cas9 system for multiplex genome editing in rice. J Genet Genomics. 2015; 42(12): 703-706. doi: 10.1016/j.jgg.2015.09.011 PMID: 26743988
41. Ikeda T, Tanaka W, Mikami M, Endo M, Hirano HY. Generation of artificial drooping leaf mutants by CRISPR-Cas9 technology in rice. Genes Genet Syst. 2016; 90(4): 231-235. doi: 10.1266/ggs.15-00030 PMID: 26617267
42. Liang Z, Zhang K, Chen K, Gao C. Targeted mutagenesis in Zea mays using TALENs and the CRISPR/ Cas system. J Genet Genomics. 2014; 41(2): 63-68. doi: 10.1016/j.jgg.2013.12.001 PMID: 24576457
43. Feng C, Yuan J, Wang R, Liu Y, Birchler JA, Han F. Efficient targeted genome modification in maize using CRISPR/Cas9 system. J Genet Genomics. 2016; 43(1): 37-43. doi: 10.1016/j.jgg.2015.10.002 PMID: 26842992
44. Zhu J, Song N, Sun S, Yang W, Zhao H, Song W, et al. Efficiency and inheritance of targeted mutagenesis in maize using CRISPR-Cas9. J Genet Genomics. 2016; 43(1): 25-36. doi: 10.1016/j.jgg.2015.10. 006 PMID: 26842991
45. Svitashev S, Young JK, Schwartz C, Gao H, Falco SC, Cigan AM. Targeted mutagenesis, precise gene editing, and site-specific gene insertion in maize using Cas9 and guide RNA. Plant Physiol. 2015; 169 (2): 931-945. doi: 10.1104/pp.15.00793 PMID: 26269544
46. Upadhyay SK, Kumar J, Alok A, Tuli R. RNA-guided genome editing for target gene mutations in wheat. G3. 2013; 3(12): 2233-2238. doi: 10.1534/g3.113.008847 PMID: 24122057
47. Wang Y, Cheng X, Shan Q, Zhang Y, Liu J, Gao C, et al. Simultaneous editing of three homoeoalleles in hexaploid bread wheat confers heritable resistance to powdery mildew. Nat Biotechnol. 2014; 32(9): 947-951. doi: 10.1038/nbt.2969 PMID: 25038773
48. Brooks C, Nekrasov V, Lippman ZB, Van Eck J. Efficient gene editing in tomato in the first generation using the clustered regularly interspaced short palindromic repeats/CRISPR-associated9 system. Plant Physiol. 2014; 166(3): 1292-1297. doi: 10.1104/pp.114.247577 PMID: 25225186
49. Ito Y, Nishizawa-Yokoi A, Endo M, Mikami M, Toki S. CRISPR/Cas9-mediated mutagenesis of the RIN locus that regulates tomato fruit ripening. Biochem Biophys Res Commun. 2015; 467(1): 76-82. doi: 10.1016/j.bbrc.2015.09.117 PMID: 26408904
50. Jacobs TB, LaFayette PR, Schmitz RJ, Parrott WA. Targeted genome modifications in soybean with CRISPR/Cas9. BMC biotechnol. 2015; 15: 16. doi: 10.1186/s12896-015-0131-2 PMID: 25879861
51. Du H, Zeng X, Zhao M, Cui X, Wang Q, Yang H, et al. Efficient targeted mutagenesis in soybean by TALENs and CRISPR/Cas9. J Biotechnol. 2016; 217: 90-97. doi: 10.1016/j.jbiotec.2015.11.005 PMID: 26603121
52. Li Z, Liu ZB, Xing A, Moon BP, Koellhoffer JP, Huang L, et al. Cas9-guide RNA directed genome editing in soybean. Plant Physiol. 2015; 169(2): 960-970. doi: 10.1104/pp.15.00783 PMID: 26294043
53. Wang S, Zhang S, Wang W, Xiong X, Meng F, Cui X. Efficient targeted mutagenesis in potato by the CRISPR/Cas9 system. Plant Cell Rep. 2015; 34(9): 1473-1476. doi: 10.1007/s00299-015-1816-7 PMID: 26082432
54. Symington LS, Gautier J. Double-strand break end resection and repair pathway choice. Annu Rev Genet. 2011; 45: 247-271. doi: 10.1146/annurev-genet-110410-132435 PMID: 21910633
55. Shukla VK, Doyon Y, Miller JC, DeKelver RC, Moehle EA, Worden SE, et al. Precise genome modification in the crop species Zea mays using zinc-finger nucleases. Nature. 2009; 459(7245): 437-441. doi: 10.1038/nature07992 PMID: 19404259
56. Li T, Liu B, Spalding MH, Weeks DP, Yang B. High-efficiency TALEN-based gene editing produces disease-resistant rice. Nat Biotechnol. 2012; 30(5): 390-392. doi: 10.1038/nbt.2199 PMID: 22565958
57. Wendt T, Holm PB, Starker CG, Christian M, Voytas DF, Brinch-Pedersen H, et al. TAL effector nucleases induce mutations at a pre-selected location in the genome of primary barley transformants. Plant Mol Biol. 2013; 83(3): 279-285. doi: 10.1007/s11103-013-0078-4 PMID: 23689819
58. Haun W, Coffman A, Clasen BM, Demorest ZL, Lowy A, Ray E, et al. Improved soybean oil quality by targeted mutagenesis of the fatty acid desaturase 2 gene family. Plant Biotechnol J. 2014; 12(7): 934-940. doi: 10.1111/pbi.12201 PMID: 24851712
59. Clasen BM, Stoddard TJ, Luo S, Demorest ZL, Li J, Cedrone F, et al. Improving cold storage and processing traits in potato through targeted gene knockout. Plant Biotechnol J. 2016; 14: 169-176. doi: 10.1111/pbi.12370 PMID: 25846201
60. Shan Q, Zhang Y, Chen K, Zhang K, Gao C. Creation of fragrant rice by targeted knockout of the OsBADH2 gene using TALEN technology. Plant Biotechnol J. 2015; 13: 791-800. doi: 10.1111/pbi. 12312 PMID: 25599829
61. Li W, Lei C, Cheng Z, Jia Y, Huang D, Wang J, et al. Identification of SSR markers for a broad-spectrum blast resistance gene Pi20(t) for marker-assisted breeding. Mol Breeding. 2008; 22(1): 141-149.
62. Hiei Y, Ohta S, Komari T, Kumashiro T. Efficient transformation of rice (Oryza sativa L.) mediated by Agrobacterium and sequence analysis of the boundaries of the T-DNA. Plant J. 1994; 6(2): 271-282. PMID: 7920717
63. Zhang Y, Su J, Duan S, Ao Y, Dai J, Liu J, et al. A highly efficient rice green tissue protoplast system for transient gene expression and studying light/chloroplast-related processes. Plant Methods. 2011; 7(1): 30. doi: 10.1186/1746-4811-7-30 PMID: 21961694
64. Shan Q, Wang Y, Chen K, Liang Z, Li J, Zhang Y, et al. Rapid and efficient gene modification in rice and Brachypodium using TALENs. Mol Plant. 2013; 6(4): 1365-1368. doi: 10.1093/mp/sss162 PMID: 23288864
65. Dellaporta SL, Wood J, Hicks JB. A plant DNA minipreparation: version II3. Plant Mol Biol Rep. 1983; 1 (4): 19-21.
66. Ma X, Chen L, Zhu Q, Chen Y, Liu YG. Rapid decoding of sequence-specific nuclease-induced heterozygous and biallelic mutations by direct sequencing of PCR products. Mol Plant. 2015; 8(8): 1285-1287. doi: 10.1016/j.molp.2015.02.012 PMID: 25747846
67. Liu W, Xie X, Ma X, Li J, Chen J, Liu YG. DSDecode: a web-based tool for decoding of sequencing chromatograms for genotyping of targeted mutations. Mol Plant. 2015; 8(9): 1431-1433. doi: 10.1016/ j.molp.2015.05.009 PMID: 26032088
68. Fukuoka S, Saka N, Koga H, Ono K, Shimizu T, Ebana K, et al. Loss of function of a proline-containing protein confers durable disease resistance in rice. Science. 2009; 325(5943): 998-1001. doi: 10.1126/ science.1175550 PMID: 19696351
69. Ma J, Lei C, Xu X, Hao K, Wang J, Cheng Z, et al. Pi64, encoding a novel CC-NBS-LRR protein, confers resistance toleaf and neck blast in rice. Mol Plant-Microbe Interact. 2015; 28(5): 558-568. doi: 10. 1094/MPMI-11-14-0367-R PMID: 25650828
70. Kobayashi N, Yanoria MJT, Fukuta Y. Differential varieties bred at IRRI and virulence analysis of blast isolates from the Philippines. JIRCAS Working Rep. 2007; 53: 17-30.
71. Xie K, Zhang J, Yang Y. Genome-wide prediction of highly specific guide RNA spacers for CRISPR-Cas9-mediated genome editing in model plants and major crops. Mol Plant. 2014; 7(5): 923-926. doi: 10.1093/mp/ssu009 PMID: 24482433
72. Wang M, Liu Y, Zhang C, Liu J, Liu X, Wang L, et al. Gene editing by co-transformation of TALEN and chimeric RNA/DNA oligonucleotides on the rice OsEPSPS gene and the inheritance of mutations. Plos One. 2015; 10(4): e0122755. doi: 10.1371/journal.pone.0122755 PMID: 25856577
73. Zhang H, Gou F, Zhang J, Liu W, Li Q, Mao Y, et al. TALEN-mediated targeted mutagenesis produces a large variety of heritable mutations in rice. Plant Biotechnol J. 2016; 14: 186-194. doi: 10.1111/pbi. 12372 PMID: 25867543
74. Feng Z, Mao Y, Xu N, Zhang B, Wei P, Yang DL, et al. Multigeneration analysis reveals the inheritance, specificity, and patterns of CRISPR/Cas-induced gene modifications in Arabidopsis. Proc Natl Acad Sci USA. 2014; 111(12): 4632-4637. doi: 10.1073/pnas.1400822111 PMID: 24550464
75. Lowder LG, Zhang D, Baltes NJ, Paul JW III, Tang X, Zheng X, et al. A CRISPR/Cas9 toolbox for multiplexed plant genome editing and transcriptional regulation. Plant Physiol. 2015; 169(2): 971-985. doi: 10.1104/pp.15.00636 PMID: 26297141
76. Cermak T, Doyle EL, Christian M, Wang L, Zhang Y, Schmidt C, et al. Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic Acids Res. 2011; 39(12): e82. doi: 10.1093/nar/gkr218 PMID: 21493687
77. Huang P, Xiao A, Zhou M, Zhu Z, Lin S, Zhang B. Heritable gene targeting in zebrafish using customized TALENs. Nat Biotechnol. 2011; 29(8): 699-700. doi: 10.1038/nbt.1939 PMID: 21822242
78. Li T, Huang S, Zhao X, Wright DA, Carpenter S, Spalding MH, et al. Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes. Nucleic Acids Res. 2011; 39(14): 6315-6325. doi: 10.1093/nar/gkr188 PMID: 21459844
79. Hruscha A, Krawitz P, Rechenberg A, Heinrich V, Hecht J, Haass C, et al. Efficient CRISPR/Cas9 genome editing with low off-target effects in zebrafish. Development. 2013; 140(24): 4982-4987. doi: 10.1242/dev.099085 PMID: 24257628
80. Fu Y, Foden JA, Khayter C, Maeder ML, Reyon D, Joung JK, et al. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat Biotechnol. 2013; 31(9): 822-826. doi: 10. 1038/nbt.2623 PMID: 23792628
81. Lin YN, Cradick TJ, Brown MT, Deshmukh H, Ranjan P, Sarode N, et al. CRISPR/Cas9 systems have off-target activity with insertions or deletions between target DNA and guide RNA sequences. Nucleic Acids Res. 2014; 42(11): 7473-7485. doi: 10.1093/nar/gku402 PMID: 24838573
82. Mussolino C, Morbitzer R, Lutge F, Dannemann N, Lahaye T, Cathomen T. A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity. Nucleic Acids Res. 2011; 39(21): 9283-9293. doi: 10.1093/nar/gkr597 PMID: 21813459
83. Wang X, Wang Y, Wu X, Wang J, Wang Y, Qiu Z, et al. Unbiased detection of off-target cleavage by CRISPR-Cas9 and TALENs using integrase-defective lentiviral vectors. Nat Biotechnol. 2015; 33(2): 175-178. doi: 10.1038/nbt.3127 PMID: 25599175