Research Progress in Off-target in CRISPR/Cas9 Genome Editing
Received date: 2018-01-03
Accepted date: 2018-03-29
Online published: 2018-09-11
CRISPR/Cas9 technology has rapidly developed in recent years. It is widely used for study of animals, plants and microorganisms. Among all developments, the use of the technology for the off-target issue has progressed, with important breakthroughs for this hot topic. This paper elucidates the principle of off-target generation and the method for detecting off target both in vitro and in vivo. Also, how to reduce off-targets by improving single-guide RNA design and optimizing the CRISPR system is evaluated. Further more, detecting off-targets at the right time and improving the precision and accuracy of off-target detection are proposed for plant site-specific genome editing.
Key words： CRISPR/Cas9; site specific editing; off-target
Wang Ying, Li Xianggan, Qiu Lijuan . Research Progress in Off-target in CRISPR/Cas9 Genome Editing[J]. Chinese Bulletin of Botany, 2018 , 53(4) : 528 -541 . DOI: 10.11983/CBB18004
| 1 | Bae S, Park J, Kim JS (2014). Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases.Bioinformatics 30, 1473-1475. |
| 2 | Belhaj K, Chaparro-Garcia A, Kamoun S, Nekrasov V (2013). Plant genome editing made easy: targeted muta- genesis in model and crop plants using the CRISPR/Cas system.Plant Methods 9, 39. |
| 3 | Cameron P, Fuller CK, Donohoue PD, Jones BN, Thom- pson MS, Carter MM, Gradia S, Vidal B, Garner E, Slorach EM, Lau E, Banh LM, Lied AM, Edwards LS, Settle AH, Capurso D, Llaca V, Deschamps S, Cigan M, Young JK, May AP (2017). Mapping the genomic landscape of CRISPR-Cas9 cleavage.Nat Methods 14, 600-606. |
| 4 | Cencic R, Miura H, Malina A, Robert F, Ethier S, Schme- ing TM, Dostie J, Pelletier J (2014). Protospacer adjacent motif (PAM)-distal sequences engage CRISPR Cas9 DNA target cleavage.PLoS One 9, e109213. |
| 5 | Chari R, Mali P, Moosburner M, Church GM (2015). Unraveling CRISPR-Cas9 genome engineering parameters via a library-on-library approach.Nat Methods 12, 823-826. |
| 6 | Chen XG, Lu XK, Shu N, Wang S, Wang JJ, Wang DL, Guo LX, Ye WW (2017). Targeted mutagenesis in cotton (Gossypium hirsutum L.) using the CRISPR/Cas9 system. Sci Rep 7, 44304. |
| 7 | Chiarle R, Zhang Y, Frock RL, Lewis SM, Molinie B, Ho YJ, Myers DR, Choi VW, Compagno M, Malkin DJ, Neuberg D, Monti S, Giallourakis CC, Gostissa M, Alt FW (2011). Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells. Cell 147, 107-119. |
| 8 | Cho SW, Kim S, Kim Y, Kweon J, Kim HS, Bae S, Kim JS (2014). Analysis of off-target effects of CRISPR/Cas- derived RNA-guided endonucleases and nickases.Genome Res 24, 132-141. |
| 9 | Cradick TJ, Fine EJ, Antico CJ, Bao G (2013). CRISPR/ Cas9 systems targeting β-globin and CCR5 genes have substantial off-target activity. Nucleic Acids Res 41, 9584-9592. |
| 10 | Crosetto N, Mitra A, Silva MJ, Bienko M, Dojer N, Wang Q, Karaca E, Chiarle R, Skrzypczak M, Ginalski K, Pasero P, Rowicka M, Dikic I (2013). Nucleotide-resolution DNA double-strand break mapping by next-generation sequen- cing.Nat Methods 10, 361-365. |
| 11 | Deveau H, Garneau JE, Moineau S (2010). CRISPR/Cas system and its role in phage-bacteria interactions.Annu Rev Microbiol 64, 475-493. |
| 12 | Doench JG, Fusi N, Sullender M, Hegde M, Vaimberg EW, Donovan KF, Smith I, Tothova Z, Wilen C, Orchard R, Virgin HW, Listgarten J, Root DE (2016). Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9.Nat Biotechnol 34, 184-191. |
| 13 | Duan JZ, Lu GQ, Xie Z, Lou ML, Luo J, Guo L, Zhang Y (2014). Genome-wide identification of CRISPR/Cas9 off- targets in human genome.Cell Res 24, 1009-1012. |
| 14 | Friedland AE, Baral R, Singhal P, Loveluck K, Shen S, Sanchez M, Marco E, Gotta GM, Maeder ML, Kennedy EM, Kornepati AV, Sousa A, Collins MA, Jayaram H, Cullen BR, BumcrotEmail D (2015). Characterization of Staphylococcus aureus Cas9: a smaller Cas9 for all-in-one adeno-associated virus delivery and paired nickase applications. Genome Biol 16, 257. |
| 15 | Frock RL, Hu JZ, Meyers RM, Ho YJ, Kii E, Alt FW (2015). Genome-wide detection of DNA double-stranded breaks induced by engineered nucleases.Nat Biotechnol 33, 179-186. |
| 16 | Fu YF, Foden JA, Khayter C, Maeder ML, Reyon D, Joung JK, Sander JD (2013). High-frequency off-target mutag- enesis induced by CRISPR-Cas nucleases in human cells.Nat Biotechnol 31, 822-826. |
| 17 | Fu YF, Sander JD, Reyon D, Cascio VM, Joung JK (2014). Improving CRISPR-Cas nuclease specificity using truncated guide RNAs.Nat Biotechnol 32, 279-284. |
| 18 | Gabriel R, Lombardo A, Arens A, Miller JC, Genovese P, Kaeppel C, Nowrouzi A, Bartholomae CC, Wang JB, Friedman G, Holmes MC, Gregory PD, Glimm H, Schmidt M, Naldini L, von Kalle C (2011). An unbiased genome-wide analysis of zinc-finger nuclease specificity.Nat Biotechnol 29, 816-823. |
| 19 | Harrington LB, Doxzen KW, Ma E, Liu JJ, Knott GJ, Edraki A, Garcia B, Amrani N, Chen JS, Cofsky JC, Kranzusch PJ, Sontheimer EJ, Davidson AR, Maxwell KL, Doudna JA (2017). A broad-spectrum inhibitor of CRISPR-Cas9.Cell 170, 1224-1233. |
| 20 | Havlicek S, Shen Y, Alpagu Y, Bruntraeger MB, Zufir NBM, Phuah ZY, Fu ZY, Dunn NR, Stanton LW (2017). Re-engineered RNA-guided fokI-nucleases for improved genome editing in human cells.Mol Ther 25, 342-355. |
| 21 | Hsu PD, Lander ES, Zhang F (2014). Development and applications of CRISPR-Cas9 for genome engineering.Cell 157, 1262-1278. |
| 22 | Hsu PD, Scott DA, Weinstein JA, Ran FA, Konermann S, Agarwala V, Li YQ, Fine EJ, Wu XB, Shalem O, Cradick TJ, Marraffini LA, Bao G, Zhang F (2013). DNA targeting specificity of RNA-guided Cas9 nucleases.Nat Biotechnol 31, 827-832. |
| 23 | Jiang WY, Bikard D, Cox D, Zhang F, Marraffini LA (2013). RNA-guided editing of bacterial genomes using CRISPR- Cas systems.Nat Biotechnol 31, 233-239. |
| 24 | Jiang WZ, Yang B, Weeks DP (2014). Efficient CRISPR/ Cas9-mediated gene editing in Arabidopsis thaliana and inheritance of modified genes in the T2 and T3 generations. PLoS One 9, e99225. |
| 25 | Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012). A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.Science 337, 816-821. |
| 26 | Joung KJ, Tsai S (2017a). Full interrogation of nuclease DSBS and sequencing (find-seq). USA, 20170073747. 2017-03-16. |
| 27 | Joung KJ, Tsai S (2017b). Comprehensive in vitro reporting of cleavage events by sequencing (circle-seq). USA, 9850- 484. 2017-12-26. |
| 28 | Kaya H, Mikami M, Endo A, Endo M, Toki S (2016). Highly specific targeted mutagenesis in plants using Staphylococcus aureus Cas9. Sci Rep 6, 26871. |
| 29 | Kim D, Bae S, Park J, Kim E, Kim S, Yu HR, Hwang J, Kim JI, Kim JS (2015). Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells.Nat Methods 12, 237-243. |
| 30 | Kim D, Kim S, Kim S, Park J, Kim JS (2016). Genome-wide target specificities of CRISPR-Cas9 nucleases revealed by multiplex Digenome-seq.Genome Res 26, 406-415. |
| 31 | Kleinstiver BP, Pattanayak V, Prew MS, Tsai SQ, Nguyen NT, Zheng ZL, Joung JK (2016). High-fidelity CRISPR- Cas9 nucleases with no detectable genome-wide off-target effects.Nature 529, 490-495. |
| 32 | Kleinstiver BP, Prew MS, Tsai SQ, Nguyen NT, Topkar VV, Zheng ZL, Joung JK (2015a). Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition. Nat Biotechnol 33, 1293-1298. |
| 33 | Kleinstiver BP, Prew MS, Tsai SQ, Topkar VV, Nguyen NT, Zheng ZL, Gonzales APW, Li ZY, Peterson RT, Yeh JRJ, Aryee MJ, Joung JK (2015b). Engineered CRISPR- Cas9 nucleases with altered PAM specificities.Nature 523, 481-485. |
| 34 | Kuscu C, Arslan S, Singh R, Thorpe J, Adli M (2014). Genome-wide analysis reveals characteristics of off-target sites bound by the Cas9 endonuclease.Nat Biotechnol 32, 677-683. |
| 35 | Lee CM, Cradick TJ, Fine EJ, Bao G (2016). Nuclease target site selection for maximizing on-target activity and minimizing off-target effects in genome editing.Mol Ther 24, 475-487. |
| 36 | Lee JK, Jeong E, Lee J, Jung M, Shin E, Kim YH, Lee K, Kim D, Kim S, Kim JS (2017). Directed evolution of CRISPR- Cas9 to increase its specificity.bioRxiv (1), 237040. |
| 37 | Li JC, Wang XB, Song WW, Huang XY, Zhou J, Zeng HY, Sun S, Jia HC, Li WB, Zhou XA, Li SZ, Chen PY, Wu CX, Guo Y, Han TF, Qiu LJ (2017). Genetic variation of maturity groups and four E genes in the Chinese soybean mini core collection. PLoS One 12, e0172106. |
| 38 | Li W, Teng F, Li TD, Zhou Q (2013). Simultaneous generation and germline transmission of multiple gene mutations in rat using CRISPR-Cas systems.Nat Biotechnol 31, 684-686. |
| 39 | Lozano-Juste J, Cutler SR (2014). Plant genome engineering in full bloom.Trends Plant Sci 19, 284-287. |
| 40 | Mali P, Yang LH, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM (2013). RNA-guided human genome engineering via Cas9.Science 339, 823-826. |
| 41 | Meng XB, Hu XX, Liu Q, Song XG, Gao CX, Li JY, Wang KJ (2018). Robust genome editing of CRISPR-Cas9 at NAG PAMs in rice.Sci China Life Sci 61, 122-125. |
| 42 | Montague TG, Cruz JM, Gagnon JA, Church GM, Valen E (2014). CHOPCHOP: a CRISPR/Cas9 and TALEN web tool for genome editing.Nucleic Acids Res 42, W401-W407. |
| 43 | Osakabe Y, Watanabe T, Sugano SS, Ueta R, Ishihara R, Shinozaki K, Osakabe K (2016). Optimization of CRISPR/ Cas9 genome editing to modify abiotic stress responses in plants.Sci Rep 6, 26685. |
| 44 | Osborn MJ, Webber BR, Knipping F, Lonetree CL, Tennis N, DeFeo AP, McElroy AN, Starker CG, Lee C, Merkel S, Lund TC, Kelly-Spratt KS, Jensen MC, Voytas DF, von Kalle C, Schmidt M, Gabriel R, Hippen KL, Miller JS, Scharenberg AM, Tolar J, Blazar BR (2016). Eval- uation of TCR gene editing achieved by TALENs, CRISPR/ Cas9, and megaTAL nucleases.Mol Ther 24, 570-581. |
| 45 | Pan CT, Ye L, Qin L, Liu X, He YJ, Wang J, Chen LF, Lu G (2016). CRISPR/Cas9-mediated efficient and heritable targeted mutagenesis in tomato plants in the first and later generations.Sci Rep 6, 24765. |
| 46 | Pattanayak V, Lin S, Guilinger JP, Ma E, Doudna JA, Liu DR (2013). High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity.Nat Biotechnol 31, 839-843. |
| 47 | Peterson BA, Haak DC, Nishimura MT, Teixeira PJPL, James SR, Dangl JL, Nimchuk ZL (2016). Genome-wide assessment of efficiency and specificity in CRISPR/Cas9 mediated multiple site targeting in Arabidopsis.PLoS One 11, e0162169. |
| 48 | Pourcel C, Drevet C (2013). Occurrence, diversity of CRISPR- Cas systems and genotyping implications. In: Barrangou R, van der Oost J, eds. CRISPR-Cas Systems. Berlin: Springer. pp. 33-59. |
| 49 | Prykhozhij SV, Rajan V, Gaston D, Berman JN (2015). CRISPR multitargeter: a web tool to find common and unique CRISPR single guide RNA targets in a set of similar sequences.PLoS One 10, e0119372. |
| 50 | Sampson TR, Weiss DS (2013). Alternative roles for CRISPR/Cas systems in bacterial pathogenesis.PLoS Pa- thog 9, e1003621. |
| 51 | Shen B, Zhang WS, Zhang J, Zhou JK, Wang JY, Chen L, Wang L, Hodgkins A, Iyer V, Huang XX, Skarnes WC (2014). Efficient genome modification by CRISPR-Cas9 nickase with minimal off-target effects.Nat Methods 11, 399-402. |
| 52 | Shen CX, Que ZQ, Xia YM, Tang N, Li D, He RH, Cao ML (2017). Knock out of the annexin gene OsAnn3 via CRISPR/Cas9-mediated genome editing decreased cold tolerance in rice. J Plant Biol 60, 539-547. |
| 53 | Shin J, Jiang FG, Liu JJ, Bray NL, Rauch BJ, Baik SH, Nogales E, Bondy-Denomy J, Corn JE, Doudna JA (2017). Disabling Cas9 by an anti-CRISPR DNA mimic.Sci Adv 3, e1701620. |
| 54 | Slaymaker IM, Gao LY, Zetsche B, Scott DA, Yan WX, Zhang F (2016). Rationally engineered Cas9 nucleases with improved specificity.Science 351, 84-88. |
| 55 | Smith C, Gore A, Yan W, Abalde-Atristain L, Li Z, He CX, Wang Y, Brodsky RA, Zhang K, Cheng LZ, Ye ZH (2014). Whole-genome sequencing analysis reveals high specificity of CRISPR/Cas9 and TALEN-based genome editing in human iPSCs.Cell Stem Cell 15, 12-13. |
| 56 | Tian SW, Jiang LJ, Gao Q, Zhang J, Zong M, Zhang HY, Ren Y, Guo SG, Gong GY, Liu F, Xu Y (2017). Efficient CRISPR/Cas9-based gene knockout in watermelon.Plant Cell Rep 36, 399-406. |
| 57 | Tsai SQ, Nguyen NT, Malagon-Lopez J, Topkar VV, Aryee MJ, Joung JK (2017). CIRCLE-seq: a highly sensitive in vitro screen for genome-wide CRISPR-Cas9 nuclease off-targets. Nat Methods 14, 607-614. |
| 58 | Tsai SQ, Zheng Zl, Nguyen NT, Liebers M, Topkar VV, Thapar V, Wyvekens N, Khayter C, Iafrate AJ, Le LP, Aryee MJ, Joung JK (2015). GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases.Nat Biotechnol 33, 187-197. |
| 59 | Veres A, Gosis BS, Ding QR, Collins R, Ragavendran A, Brand H, Erdin S, Cowan CA, Talkowski ME, Musunuru K (2014). Low incidence of off-target mutations in individual CRISPR-Cas9 and TALEN targeted human stem cell clones detected by whole-genome sequencing.Cell Stem Cell 15, 27-30. |
| 60 | Wang T, Wei JJ, Sabatini DM, Lander ES (2014). Genetic screens in human cells using the CRISPR-Cas9 system.Science 343, 80-84. |
| 61 | Wang XL, Wang YB, Wu XW, Wang JH, Wang YJ, Qiu ZJ, Chang T, Huang H, Lin RJ, Yee JK (2015). Unbiased detection of off-target cleavage by CRISPR-Cas9 and TALENs using integrase-defective lentiviral vectors.Nat Biotechnol 33, 175-178. |
| 62 | Wang Y, Geng LZ, Yuan ML, Wei J, Jin C, Li M, Yu K, Zhang Y, Jin HB, Wang E, Chai ZJ, Fu XD, Li XG (2017). Deletion of a target gene in indica rice via CRISPR/Cas9. Plant Cell Rep 36, 1333-1343. |
| 63 | Wu XB, Scott DA, Kriz AJ, Chiu AC, Hsu PD, Dadon DB, Cheng AW, Trevino AE, Konermann S, Chen SD, Jaenisch R, Zhang F, Sharp PA (2014). Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells.Nat Biotechnol 32, 670-676. |
| 64 | Xu C, Ren YH, Jian YQ, Guo ZF, Zhang Y, Xie CX, Fu JJ, Wang HW, Wang GY, Xu YB, Li P, Zou C (2017). Deve- lopment of a maize 55 K SNP array with improved genome coverage for molecular breeding.Mol Breed 37, 20. |
| 65 | Xu RF, Li H, Qin RY, Wang L, Li L, Wei PC, Yang JB (2014). Gene targeting using the Agrobacterium tumefaciens-mediated CRISPR-Cas system in rice. Rice 7, 5. |
| 66 | Zhang DB, Zhang HW, Li TD, Chen KL, Qiu JL, Gao CX (2017a). Perfectly matched 20-nucleotide guide RNA sequences enable robust genome editing using high-fidelity SpCas9 nucleases.Genome Biol 18, 191. |
| 67 | Zhang H, Zhang JS, Wei PL, Zhang BT, Gou F, Feng ZY, Mao YF, Yang L, Zhang H, Xu NF, Zhu JK (2014). The CRISPR/Cas9 system produces specific and homozygous targeted gene editing in rice in one generation.Plant Biotechnol J 12, 797-807. |
| 68 | Zhang Q, Xing HL, Wang ZP, Zhang HY, Yang F, Zhou Y, Wang XC, Chen QJ (2017b). High-frequency off-target mutagenesis induced by CRISPR/Cas9 in Arabidopsis and its prevention by improving specificity of the tools.bioRxiv (1), 203489. |
| 69 | Zong Y, Wang YP, Li C, Zhang R, Chen KL, Ran YD, Qiu JL, Wang DW, Gao CX (2017). Precise base editing in rice, wheat and maize with a Cas9-cytidine deaminase fusion.Nat Biotechnol 35, 438-440. |
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