Swiftly Evolving CRISPR Genome Editing: A Revolution in Genetic Engineering
for Developing Stress-Resilient Crops

Naghmeh      Nejat; Yong      Han; Xiao-Qi      Zhang; Tianhua      He; Penghao      Wang; Chengdao      Li
Abstract

Environmental stresses adversely impact crop production, crop quality, and product safety. Climate change is predicted to exacerbate the impacts of stresses on current cropping systems with multilateral impacts on crop productivity and yield, biodiversity, soil fertility, microbial activity, and carbon sequestration. Transforming crop production systems and developing stress and climate- resilient crops are paramount to alleviate pervasive food and nutrition security and food safety issues and achieve a world free from hunger and malnutrition. Modern breeding techniques have been the key to transforming crop production systems and developing stress- and climate-resilient crops. As a rapidly evolving technology, the Nobel Prize-winning CRISPR method is a leading choice for genome editing and a possible major contributor to solving environmental and food insecurity issues. Here, a background on the stressors with far-reaching impacts on food security has been provided, and the principles and advances in classical genome editing (CRISPR/Cas9) that generate DNA double-strand breaks (DSB) have been reviewed. Base editing and prime editing platforms, which are DSB- and template-free, enabling targeted base substitutions, have been discussed. The application of such tools for trait improvement has been evaluated to develop stressresilient crops and high-throughput mutant libraries. Recent developments in the regulatory landscape for genome-edited crops in various countries have been examined. Finally, the challenges and future perspectives toward crop improvement have been highlighted.
Keywords: Abiotic stress, biotic stress, CRISPR/Cas, precision genome editing, trait improvement, regulatory landscape.
Graphical Abstract

[1] 
FAO, I., UNICEF, WFP and WHO. Transforming food systems for affordable healthy diets. In: The State of Food Security and Nutrition in the World 2020; FAO: Rome, 2020. 
[2] 
Chakraborty, S.; Newton, A.C. Climate change, plant diseases and food security: An overview. Plant Pathol.,  2011, 60(1), 2-14.
[http://dx.doi.org/10.1111/j.1365-3059.2010.02411.x] 
[3] 
Ficke, A.; Cowger, C.; Bergstrom, G.; Brodal, G. Understanding yield loss and pathogen biology to improve disease management: Septoria nodorum blotch - A case study in wheat. Plant Dis.,  2018, 102(4), 696-707.
[http://dx.doi.org/10.1094/PDIS-09-17-1375-FE] [PMID:  30673402] 
[4] 
Andjelkovic, V. Climate changes and abiotic stress in plants. In: Plant, abiotic stress and responses to climate change; InTech: London, UK, 2018; pp. 1-6.
[5] 
Butcher, K.; Wick, A.F.; DeSutter, T.; Chatterjee, A.; Harmon, J. Soil salinity: A threat to global food security. Agron. J.,  2016, 108(6), 2189-2200.
[http://dx.doi.org/10.2134/agronj2016.06.0368] 
[6] 
Fasani, E.; Manara, A.; Martini, F.; Furini, A.; DalCorso, G. The potential of genetic engineering of plants for the remediation of soils con-taminated with heavy metals. Plant Cell Environ.,  2018, 41(5), 1201-1232.
[http://dx.doi.org/10.1111/pce.12963] [PMID:  28386947] 
[7] 
Bita, C.E.; Gerats, T. Plant tolerance to high temperature in a changing environment: Scientific fundamentals and production of heat stress-tolerant crops. Front. Plant Sci.,  2013, 4, 273.
[http://dx.doi.org/10.3389/fpls.2013.00273] [PMID:  23914193] 
[8] 
Stocker, T.F.; Qin, D.; Plattner, G.K.; Alexander, L.V.; Allen, S.K.; Bindoff, N.L. Technical summary in climate change 2013: The physical science basis. In: Contribution of Working Group I to the Fifth Assessment Report of the Intergovernmental Panel on Climate Change; University Press: Cambridge, 2013. 
[9] 
Zhao, C.; Liu, B.; Piao, S.; Wang, X.; Lobell, D.B.; Huang, Y.; Huang, M.; Yao, Y.; Bassu, S.; Ciais, P.; Durand, J.L.; Elliott, J.; Ewert, F.; Janssens, I.A.; Li, T.; Lin, E.; Liu, Q.; Martre, P.; Müller, C.; Peng, S.; Peñuelas, J.; Ruane, A.C.; Wallach, D.; Wang, T.; Wu, D.; Liu, Z.; Zhu, Y.; Zhu, Z.; Asseng, S. Temperature increase reduces global yields of major crops in four independent estimates. Proc. Natl. Acad. Sci. USA,  2017, 114(35), 9326-9331.
[http://dx.doi.org/10.1073/pnas.1701762114] [PMID:  28811375] 
[10] 
Pachauri, RK Climate change 2007: Synthesis report. Contribution of Working Groups I, II and III to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change; Geneva, Switzerland, 2007. 
[11] 
Field, C.B.; Barros, V.R.; Dokken, D.J.; Mach, K.J.; Mastrandrea, M.D.; Bilir, T.E. Summary for policymakers.in Climate Change 2014: Impacts, adaptation, and vulnerability. In: Part A: Global and Sectoral Aspects. Contribution of Working Group II to the Fifth Assessment Report of the Intergovernmental Panel on Climate Change; Cambridge University Press: New York, NY, 2014. 
[12] 
Christidis, N.; Jones, G.S.; Stott, P.A. Dramatically increasing chance of extremely hot summers since the 2003 European heatwave. Nat. Clim. Chang.,  2015, 5(1), 46-50.
[http://dx.doi.org/10.1038/nclimate2468] 
[13] 
Lipiec, J.; Doussan, C.; Nosalewicz, A.; Kondracka, K. Effect of drought and heat stresses on plant growth and yield: A review. Int. Agrophys.,  2013, 27(4), 463-477.
[http://dx.doi.org/10.2478/intag-2013-0017] 
[14] 
Fang, Y.; Xiong, L. General mechanisms of drought response and their application in drought resistance improvement in plants. Cell. Mol. Life Sci.,  2015, 72(4), 673-689.
[http://dx.doi.org/10.1007/s00018-014-1767-0] [PMID:  25336153] 
[15] 
Lesk, C.; Rowhani, P.; Ramankutty, N. Influence of extreme weather disasters on global crop production. Nature,  2016, 529(7584), 84-87.
[http://dx.doi.org/10.1038/nature16467] [PMID:  26738594] 
[16] 
Burke, E.J.; Brown, S.J.; Christidis, N. Modeling the recent evolution of global drought and projections for the twenty-first century with the hadley centre climate model. J. Hydrometeorol.,  2006, 7(5), 1113-1125.
[http://dx.doi.org/10.1175/JHM544.1] 
[17] 
Tripathi, P.; Rabara, R.C.; Rushton, P.J. A systems biology perspective on the role of WRKY transcription factors in drought responses in plants. Planta,  2014, 239(2), 255-266.
[http://dx.doi.org/10.1007/s00425-013-1985-y] [PMID:  24146023] 
[18] 
Fahad, S.; Bajwa, A.A.; Nazir, U.; Anjum, S.A.; Farooq, A.; Zohaib, A.; Sadia, S.; Nasim, W.; Adkins, S.; Saud, S.; Ihsan, M.Z.; Alharby, H.; Wu, C.; Wang, D.; Huang, J. Crop production under drought and heat stress: Plant responses and management options. Front. Plant Sci.,  2017, 8, 1147.
[http://dx.doi.org/10.3389/fpls.2017.01147] [PMID:  28706531] 
[19] 
Sehgal, A.; Sita, K.; Siddique, K.H.M.; Kumar, R.; Bhogireddy, S.; Varshney, R.K. HanumanthaRao, B.; Nair, R.M.; Prasad, P.V.V.; Nayyar, H. Drought or/and heat-stress effects on seed filling in food crops: Impacts on functional biochemistry, seed yields, and nutri-tional quality. Front. Plant Sci.,  2018, 9, 1705.
[20] 
Nejat, N.; Rookes, J.; Mantri, N.L.; Cahill, D.M. Plant-pathogen interactions: Toward development of next-generation disease-resistant plants. Crit. Rev. Biotechnol.,  2017, 37(2), 229-237.
[http://dx.doi.org/10.3109/07388551.2015.1134437] [PMID:  26796880] 
[21] 
Haudry, A.; Cenci, A.; Ravel, C.; Bataillon, T.; Brunel, D.; Poncet, C.; Hochu, I.; Poirier, S.; Santoni, S.; Glémin, S.; David, J. Grinding up wheat: A massive loss of nucleotide diversity since domestication. Mol. Biol. Evol.,  2007, 24(7), 1506-1517.
[http://dx.doi.org/10.1093/molbev/msm077] [PMID:  17443011] 
[22] 
Zhu, Q.; Zheng, X.; Luo, J.; Gaut, B.S.; Ge, S. Multilocus analysis of nucleotide variation of Oryza sativa and its wild relatives: Severe bottleneck during domestication of rice. Mol. Biol. Evol.,  2007, 24(3), 875-888.
[http://dx.doi.org/10.1093/molbev/msm005] [PMID:  17218640] 
[23] 
Breseghello, F.; Coelho, A.S.G. Traditional and modern plant breeding methods with examples in rice (Oryza sativa L.). J. Agric. Food Chem.,  2013, 61(35), 8277-8286.
[http://dx.doi.org/10.1021/jf305531j] [PMID:  23551250] 
[24] 
Tao, Y.; Zhao, X.; Mace, E.; Henry, R.; Jordan, D. Exploring and exploiting pan-genomics for crop improvement. Mol. Plant,  2019, 12(2), 156-169.
[http://dx.doi.org/10.1016/j.molp.2018.12.016] [PMID:  30594655] 
[25] 
Jinek, M.; Chylinski, K.; Fonfara, I.; Hauer, M.; Doudna, J.A.; Charpentier, E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science,  2012, 337(6096), 816-821.
[http://dx.doi.org/10.1126/science.1225829] [PMID:  22745249] 
[26] 
Gaj, T.; Gersbach, C.A.; Barbas, C.F. III ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol.,  2013, 31(7), 397-405.
[http://dx.doi.org/10.1016/j.tibtech.2013.04.004] [PMID:  23664777] 
[27] 
Pyott, D.E.; Sheehan, E.; Molnar, A. Engineering of CRISPR/Cas9-mediated potyvirus resistance in transgene-free Arabidopsis plants. Mol. Plant Pathol.,  2016, 17(8), 1276-1288.
[http://dx.doi.org/10.1111/mpp.12417] [PMID:  27103354] 
[28] 
Horvath, P.; Barrangou, R. CRISPR/Cas, the immune system of bacteria and archaea. Science,  2010, 327(5962), 167-170.
[http://dx.doi.org/10.1126/science.1179555] [PMID:  20056882] 
[29] 
Bhaya, D.; Davison, M.; Barrangou, R. CRISPR-Cas systems in bacteria and archaea: Versatile small RNAs for adaptive defense and regu-lation. Annu. Rev. Genet.,  2011, 45(1), 273-297.
[http://dx.doi.org/10.1146/annurev-genet-110410-132430] [PMID:  22060043] 
[30] 
Mali, P.; Aach, J.; Stranges, P.B.; Esvelt, K.M.; Moosburner, M.; Kosuri, S.; Yang, L.; Church, G.M. CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat. Biotechnol.,  2013, 31(9), 833-838.
[http://dx.doi.org/10.1038/nbt.2675] [PMID:  23907171] 
[31] 
Nishimasu, H.; Ran, F.A.; Hsu, P.D.; Konermann, S.; Shehata, S.I.; Dohmae, N.; Ishitani, R.; Zhang, F.; Nureki, O. Crystal structure of Cas9 in complex with guide RNA and target DNA. Cell,  2014, 156(5), 935-949.
[http://dx.doi.org/10.1016/j.cell.2014.02.001] [PMID:  24529477] 
[32] 
Mladenov, E.; Iliakis, G. Induction and repair of DNA double strand breaks: The increasing spectrum of non-homologous end joining pathways. Mutat. Res.,  2011, 711(1-2), 61-72.
[http://dx.doi.org/10.1016/j.mrfmmm.2011.02.005] [PMID:  21329706] 
[33] 
Doudna, J. A.; Charpentier, E. The new frontier of genome engineering with CRISPR-Cas9. Science,  2014, 346(6213), 1258096-1-1258096-9.
[http://dx.doi.org/10.1126/science.1258096] 
[34] 
Cho, S.W.; Kim, S.; Kim, J.M.; Kim, J.S. Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat. Biotechnol.,  2013, 31(3), 230-232.
[http://dx.doi.org/10.1038/nbt.2507] [PMID:  23360966] 
[35] 
Mali, P.; Yang, L.; Esvelt, K.M.; Aach, J.; Guell, M.; DiCarlo, J.E.; Norville, J.E.; Church, G.M. RNA-guided human genome engineering via Cas9. Science,  2013, 339(6121), 823-826.
[http://dx.doi.org/10.1126/science.1232033] [PMID:  23287722] 
[36] 
Jiang, W.; Marraffini, L.A. CRISPR-cas: New tools for genetic manipulations from bacterial immunity systems. Annu. Rev. Microbiol.,  2015, 69(1), 209-228.
[http://dx.doi.org/10.1146/annurev-micro-091014-104441] [PMID:  26209264] 
[37] 
Schindele, P.; Wolter, F.; Puchta, H. Transforming plant biology and breeding with CRISPR/Cas9, Cas12 and Cas13. FEBS Lett.,  2018, 592(12), 1954-1967.
[http://dx.doi.org/10.1002/1873-3468.13073] [PMID:  29710373] 
[38] 
Feng, Z.; Zhang, B.; Ding, W.; Liu, X.; Yang, D.L.; Wei, P.; Cao, F.; Zhu, S.; Zhang, F.; Mao, Y.; Zhu, J.K. Efficient genome editing in plants using a CRISPR/Cas system. Cell Res.,  2013, 23(10), 1229-1232.
[http://dx.doi.org/10.1038/cr.2013.114] [PMID:  23958582] 
[39] 
Jiang, W.; Zhou, H.; Bi, H.; Fromm, M.; Yang, B.; Weeks, D.P. Demonstration of CRISPR/Cas9/sgRNA-mediated targeted gene modifica-tion in Arabidopsis, tobacco, sorghum and rice. Nucleic Acids Res.,  2013, 41(20), e188.
[http://dx.doi.org/10.1093/nar/gkt780] [PMID:  23999092] 
[40] 
Li, J.F.; Norville, J.E.; Aach, J.; McCormack, M.; Zhang, D.; Bush, J.; Church, G.M.; Sheen, J. Multiplex and homologous recombination-mediated genome editing in Arabidopsis and Nicotiana benthamiana using guide RNA and Cas9. Nat. Biotechnol.,  2013, 31(8), 688-691.
[http://dx.doi.org/10.1038/nbt.2654] [PMID:  23929339] 
[41] 
Nekrasov, V.; Staskawicz, B.; Weigel, D.; Jones, J.D.G.; Kamoun, S. Targeted mutagenesis in the model plant Nicotiana benthamiana us-ing Cas9 RNA-guided endonuclease. Nat. Biotechnol.,  2013, 31(8), 691-693.
[http://dx.doi.org/10.1038/nbt.2655] [PMID:  23929340] 
[42] 
Shan, Q.; Wang, Y.; Li, J.; Zhang, Y.; Chen, K.; Liang, Z.; Zhang, K.; Liu, J.; Xi, J.J.; Qiu, J.L.; Gao, C. Targeted genome modification of crop plants using a CRISPR-Cas system. Nat. Biotechnol.,  2013, 31(8), 686-688.
[http://dx.doi.org/10.1038/nbt.2650] [PMID:  23929338] 
[43] 
Upadhyay, S.K.; Kumar, J.; Alok, A.; Tuli, R. RNA-guided genome editing for target gene mutations in wheat. G3-Genes Genom Genet,  2013, 3(12), 2233-2238.
[44] 
Wang, Y.; Cheng, X.; Shan, Q.; Zhang, Y.; Liu, J.; Gao, C.; Qiu, J.L. Simultaneous editing of three homoeoalleles in hexaploid bread wheat confers heritable resistance to powdery mildew. Nat. Biotechnol.,  2014, 32(9), 947-951.
[http://dx.doi.org/10.1038/nbt.2969] [PMID:  25038773] 
[45] 
Howells, R.M.; Craze, M.; Bowden, S.; Wallington, E.J. Efficient generation of stable, heritable gene edits in wheat using CRISPR/Cas9. BMC Plant Biol.,  2018, 18(1), 215.
[http://dx.doi.org/10.1186/s12870-018-1433-z] [PMID:  30285624] 
[46] 
Xie, K.; Yang, Y. RNA-guided genome editing in plants using a CRISPR-Cas system. Mol. Plant,  2013, 6(6), 1975-1983.
[http://dx.doi.org/10.1093/mp/sst119] [PMID:  23956122] 
[47] 
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.
[http://dx.doi.org/10.1016/j.jgg.2013.12.001] [PMID:  24576457] 
[48] 
Lawrenson, T.; Shorinola, O.; Stacey, N.; Li, C.; Østergaard, L.; Patron, N.; Uauy, C.; Harwood, W. Induction of targeted, heritable muta-tions in barley and Brassica oleracea using RNA-guided Cas9 nuclease. Genome Biol.,  2015, 16(1), 258.
[http://dx.doi.org/10.1186/s13059-015-0826-7] [PMID:  26616834] 
[49] 
Gasparis, S.; Kała, M.; Przyborowski, M.; Łyżnik, L.A.; Orczyk, W.; Nadolska-Orczyk, A. A simple and efficient CRISPR/Cas9 platform for induction of single and multiple, heritable mutations in barley (Hordeum vulgare L.). Plant Methods,  2018, 14(1), 111.
[http://dx.doi.org/10.1186/s13007-018-0382-8] [PMID:  30568723] 
[50] 
Han, Y.; Broughton, S.; Liu, L.; Zhang, X.Q.; Zeng, J.; He, X.; Li, C. Highly efficient and genotype-independent barley gene editing based on anther culture. Plant Commun.,  2020, 2(2), 100082.
[http://dx.doi.org/10.1016/j.xplc.2020.100082] [PMID:  33898972] 
[51] 
Brooks, C.; Nekrasov, V.; Lippman, Z.B.; 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.
[http://dx.doi.org/10.1104/pp.114.247577] [PMID:  25225186] 
[52] 
Ron, M.; Kajala, K.; Pauluzzi, G.; Wang, D.; Reynoso, M.A.; Zumstein, K.; Garcha, J.; Winte, S.; Masson, H.; Inagaki, S.; Federici, F.; Sinha, N.; Deal, R.B.; Bailey-Serres, J.; Brady, S.M. Hairy root transformation using Agrobacterium rhizogenes as a tool for exploring cell type-specific gene expression and function using tomato as a model. Plant Physiol.,  2014, 166(2), 455-469.
[http://dx.doi.org/10.1104/pp.114.239392] [PMID:  24868032] 
[53] 
Butler, N.M.; Atkins, P.A.; Voytas, D.F.; Douches, D.S. Generation and inheritance of targeted mutations in potato (Solanum tuberosum L.) using the CRISPR/cas system. PLoS One,  2015, 10(12), e0144591.
[http://dx.doi.org/10.1371/journal.pone.0144591] [PMID:  26657719] 
[54] 
Zhang, T.; Zheng, Q.; Yi, X.; An, H.; Zhao, Y.; Ma, S.; Zhou, G. Establishing RNA virus resistance in plants by harnessing CRISPR im-mune system. Plant Biotechnol. J.,  2018, 16(8), 1415-1423.
[http://dx.doi.org/10.1111/pbi.12881] [PMID:  29327438] 
[55] 
Yin, K.H.T.; Xie, K.; Zhao, J.; Song, J.; Liu, Y. Engineer complete resistance to cotton leaf curl Multan virus by the CRISPR/Cas9 system in Nicotiana benthamiana. Phytopathology Research,  2019, 1(1), 9.
[http://dx.doi.org/10.1186/s42483-019-0017-7] 
[56] 
Paixao, J.F.R.; Gillet, F.X.; Ribeiro, T.P.; Bournaud, C.; Lourenco-Tessutti, I.T.; Noriega, D.D.; de Melo, B.P.; de Almeida-Engler, J.; Grossi-de-Sa, M.F. Improved drought stress tolerance in Arabidopsis by CRISPR/dCas9 fusion with a Histone AcetylTransferase. Sci. Rep-Uk,  2019, 9(1), 1-9.
[57] 
Langner, T.; Kamoun, S.; Belhaj, K. CRISPR crops: Plant genome editing toward disease resistance. Annu. Rev. Phytopathol.,  2018, 56(1), 479-512.
[http://dx.doi.org/10.1146/annurev-phyto-080417-050158] [PMID:  29975607] 
[58] 
Jaganathan, D.; Ramasamy, K.; Sellamuthu, G.; Jayabalan, S.; Venkataraman, G. CRISPR for crop improvement: An update review. Front. Plant Sci.,  2018, 9, 985.
[http://dx.doi.org/10.3389/fpls.2018.00985] [PMID:  30065734] 
[59] 
Li, M.; Li, X.; Zhou, Z.; Wu, P.; Fang, M.; Pan, X.; Lin, Q.; Luo, W.; Wu, G.; Li, H. Reassessment of the four yield-related genes Gn1a, DEP1, GS3, and IPA1 in rice using a CRISPR/Cas9 system. Front. Plant Sci.,  2016, 7, 377.
[http://dx.doi.org/10.3389/fpls.2016.00377] [PMID:  27066031] 
[60] 
Zeng, Y.; Wen, J.; Zhao, W.; Wang, Q.; Huang, W. Rational improvement of rice yield and cold tolerance by editing the three genes OsPIN5b, GS3, and OsMYB30 with the CRISPR-Cas9 system. Front. Plant Sci.,  2020, 10, 1663.
[http://dx.doi.org/10.3389/fpls.2019.01663] [PMID:  31993066] 
[61] 
Rodríguez-Leal, D.; Lemmon, Z.H.; Man, J.; Bartlett, M.E.; Lippman, Z.B. Engineering quantitative trait variation for crop improvement by genome editing. Cell,  2017, 171(2), 470-480.e8.
[http://dx.doi.org/10.1016/j.cell.2017.08.030] [PMID:  28919077] 
[62] 
Soyk, S.; Müller, N.A.; Park, S.J.; Schmalenbach, I.; Jiang, K.; Hayama, R.; Zhang, L.; Van Eck, J.; Jiménez-Gómez, J.M.; Lippman, Z.B. Variation in the flowering gene self pruning 5G promotes day-neutrality and early yield in tomato. Nat. Genet.,  2017, 49(1), 162-168.
[http://dx.doi.org/10.1038/ng.3733] [PMID:  27918538] 
[63] 
Ueta, R.; Abe, C.; Watanabe, T.; Sugano, S.S.; Ishihara, R.; Ezura, H.; Osakabe, Y.; Osakabe, K. Rapid breeding of parthenocarpic tomato plants using CRISPR/Cas9. Sci. Rep.,  2017, 7(1), 507.
[http://dx.doi.org/10.1038/s41598-017-00501-4] [PMID:  28360425] 
[64] 
Zhao, Y.P.; Zhang, C.S.; Liu, W.W.; Gao, W.; Liu, C.L.; Song, G.Y.; Li, W.X.; Mao, L.; Chen, B.J.; Xu, Y.B.; Li, X.H.; Xie, C.X. An alter-native strategy for targeted gene replacement in plants using a dual-sgRNA/Cas9 design. Sci. Rep.,  2016, 6, 23890.
[http://dx.doi.org/10.1038/srep23890] 
[65] 
Shi, J.; Gao, H.; Wang, H.; Lafitte, H.R.; Archibald, R.L.; Yang, M.; Hakimi, S.M.; Mo, H.; Habben, J.E. ARGOS8 variants generated by CRISPR-Cas9 improve maize grain yield under field drought stress conditions. Plant Biotechnol. J.,  2017, 15(2), 207-216.
[http://dx.doi.org/10.1111/pbi.12603] [PMID:  27442592] 
[66] 
Nieves-Cordones, M.; Mohamed, S.; Tanoi, K.; Kobayashi, N.I.; Takagi, K.; Vernet, A.; Guiderdoni, E.; Périn, C.; Sentenac, H.; Véry, A.A. Production of low-Cs+ rice plants by inactivation of the K+ transporter OsHAK1 with the CRISPR-Cas system. Plant J.,  2017, 92(1), 43-56.
[http://dx.doi.org/10.1111/tpj.13632] [PMID:  28670755] 
[67] 
Zhang, A.; Liu, Y.; Wang, F.; Li, T.; Chen, Z.; Kong, D.; Bi, J.; Zhang, F.; Luo, X.; Wang, J.; Tang, J.; Yu, X.; Liu, G.; Luo, L. Enhanced rice salinity tolerance via CRISPR/Cas9-targeted mutagenesis of the OsRR22 gene. Mol. Breed.,  2019, 39(3), 47.
[http://dx.doi.org/10.1007/s11032-019-0954-y] [PMID:  32803201] 
[68] 
Mao, X.; Zheng, Y.; Xiao, K.; Wei, Y.; Zhu, Y.; Cai, Q.; Chen, L.; Xie, H.; Zhang, J. OsPRX2 contributes to stomatal closure and improves potassium deficiency tolerance in rice. Biochem. Biophys. Res. Commun.,  2018, 495(1), 461-467.
[http://dx.doi.org/10.1016/j.bbrc.2017.11.045] [PMID:  29128357] 
[69] 
Bouzroud, S.; Gasparini, K.; Hu, G.; Barbosa, M.A.M.; Rosa, B.L.; Fahr, M.; Bendaou, N.; Bouzayen, M.; Zsögön, A.; Smouni, A.; Zouine, M. Down regulation and loss of Auxin Response Factor 4 function using CRISPR/Cas9 alters plant growth, stomatal function and improves tomato tolerance to salinity and osmotic stress. Genes (Basel),  2020, 11(3), E272.
[http://dx.doi.org/10.3390/genes11030272] [PMID:  32138192] 
[70] 
Ji, X.; Zhang, H.; Zhang, Y.; Wang, Y.; Gao, C. Establishing a CRISPR-Cas-like immune system conferring DNA virus resistance in plants. Nat. Plants,  2015, 1(10), 15144.
[http://dx.doi.org/10.1038/nplants.2015.144] [PMID:  27251395] 
[71] 
Baltes, N.J.; Hummel, A.W.; Konecna, E.; Cegan, R.; Bruns, A.N.; Bisaro, D.M.; Voytas, D.F. Conferring resistance to geminiviruses with the CRISPR-Cas prokaryotic immune system. Nat. Plants,  2015, 1(10), 15145.
[http://dx.doi.org/10.1038/nplants.2015.145] [PMID:  34824864] 
[72] 
Ali, Z.; Abulfaraj, A.; Idris, A.; Ali, S.; Tashkandi, M.; Mahfouz, M.M. CRISPR/Cas9-mediated viral interference in plants. Genome Biol.,  2015, 16(1), 238.
[http://dx.doi.org/10.1186/s13059-015-0799-6] [PMID:  26556628] 
[73] 
Chandrasekaran, J.; Brumin, M.; Wolf, D.; Leibman, D.; Klap, C.; Pearlsman, M.; Sherman, A.; Arazi, T.; Gal-On, A. Development of broad virus resistance in non-transgenic cucumber using CRISPR/Cas9 technology. Mol. Plant Pathol.,  2016, 17(7), 1140-1153.
[http://dx.doi.org/10.1111/mpp.12375] [PMID:  26808139] 
[74] 
Kis, A.; Hamar, É.; Tholt, G.; Bán, R.; Havelda, Z. Creating highly efficient resistance against wheat dwarf virus in barley by employing CRISPR/Cas9 system. Plant Biotechnol. J.,  2019, 17(6), 1004-1006.
[http://dx.doi.org/10.1111/pbi.13077] [PMID:  30633425] 
[75] 
Zhang, T.; Zhao, Y.; Ye, J.; Cao, X.; Xu, C.; Chen, B.; An, H.; Jiao, Y.; Zhang, F.; Yang, X.; Zhou, G. Establishing CRISPR/Cas13a im-mune system conferring RNA virus resistance in both dicot and monocot plants. Plant Biotechnol. J.,  2019, 17(7), 1185-1187.
[http://dx.doi.org/10.1111/pbi.13095] [PMID:  30785668] 
[76] 
Roy, A.; Zhai, Y.; Ortiz, J.; Neff, M.; Mandal, B.; Mukherjee, S.K.; Pappu, H.R. Multiplexed editing of a begomovirus genome restricts escape mutant formation and disease development. PLoS One,  2019, 14(10), e0223765.
[http://dx.doi.org/10.1371/journal.pone.0223765] [PMID:  31644604] 
[77] 
Gomez, M.A.; Lin, Z.D.; Moll, T.; Chauhan, R.D.; Hayden, L.; Renninger, K.; Beyene, G.; Taylor, N.J.; Carrington, J.C.; Staskawicz, B.J.; Bart, R.S. Simultaneous CRISPR/Cas9-mediated editing of cassava eIF4E isoforms nCBP-1 and nCBP-2 reduces cassava brown streak dis-ease symptom severity and incidence. Plant Biotechnol. J.,  2019, 17(2), 421-434.
[http://dx.doi.org/10.1111/pbi.12987] [PMID:  30019807] 
[78] 
Wang, F.; Wang, C.; Liu, P.; Lei, C.; Hao, W.; Gao, Y.; Liu, Y.G.; Zhao, K. Enhanced rice blast resistance by CRISPR/Cas9-targeted muta-genesis of the ERF transcription factor gene OsERF922. PLoS One,  2016, 11(4), e0154027.
[http://dx.doi.org/10.1371/journal.pone.0154027] [PMID:  27116122] 
[79] 
Zhang, Y.; Bai, Y.; Wu, G.; Zou, S.; Chen, Y.; Gao, C.; Tang, D. Simultaneous modification of three homoeologs of TaEDR1 by genome editing enhances powdery mildew resistance in wheat. Plant J.,  2017, 91(4), 714-724.
[http://dx.doi.org/10.1111/tpj.13599] [PMID:  28502081] 
[80] 
Nekrasov, V.; Wang, C.; Win, J.; Lanz, C.; Weigel, D.; Kamoun, S. Rapid generation of a transgene-free powdery mildew resistant tomato by genome deletion. Sci. Rep.,  2017, 7(1), 482.
[http://dx.doi.org/10.1038/s41598-017-00578-x] [PMID:  28352080] 
[81] 
Santillán Martínez, M.I.; Bracuto, V.; Koseoglou, E.; Appiano, M.; Jacobsen, E.; Visser, R.G.F.; Wolters, A.A.; Bai, Y. CRISPR/Cas9-targeted mutagenesis of the tomato susceptibility gene PMR4 for resistance against powdery mildew. BMC Plant Biol.,  2020, 20(1), 284.
[http://dx.doi.org/10.1186/s12870-020-02497-y] [PMID:  32560695] 
[82] 
Daniela, P.T.T. Q.B.; Dahlbeck, D.; Staskawicz, B. CRISPR-Cas9 mediated mutagenesis of a DMR6 ortholog in tomato confers broadspec-trum disease resistance. BioRxiv,  2016, 064824. Avalable from: 
[http://dx.doi.org/10.1101/064824] 
[83] 
Peng, A.; Chen, S.; Lei, T.; Xu, L.; He, Y.; Wu, L.; Yao, L.; Zou, X. Engineering canker-resistant plants through CRISPR/Cas9-targeted editing of the susceptibility gene CsLOB1 promoter in citrus. Plant Biotechnol. J.,  2017, 15(12), 1509-1519.
[http://dx.doi.org/10.1111/pbi.12733] [PMID:  28371200] 
[84] 
Kim, Y.A.; Moon, H.; Park, C.J. CRISPR/Cas9-targeted mutagenesis of Os8N3 in rice to confer resistance to Xanthomonas oryzae pv. ory-zae. Rice (N. Y.),  2019, 12(1), 67.
[http://dx.doi.org/10.1186/s12284-019-0325-7] [PMID:  31446506] 
[85] 
Xu, Z.; Xu, X.; Gong, Q.; Li, Z.; Li, Y.; Wang, S.; Yang, Y.; Ma, W.; Liu, L.; Zhu, B.; Zou, L.; Chen, G. Engineering broad-spectrum bac-terial blight resistance by simultaneously disrupting variable tale-binding elements of multiple susceptibility genes in rice. Mol. Plant,  2019, 12(11), 1434-1446.
[http://dx.doi.org/10.1016/j.molp.2019.08.006] [PMID:  31493565] 
[86] 
Oliva, R.; Ji, C.; Atienza-Grande, G.; Huguet-Tapia, J.C.; Perez-Quintero, A.; Li, T.; Eom, J.S.; Li, C.; Nguyen, H.; Liu, B.; Auguy, F.; Scial-lano, C.; Luu, V.T.; Dossa, G.S.; Cunnac, S.; Schmidt, S.M.; Slamet-Loedin, I.H.; Vera Cruz, C.; Szurek, B.; Frommer, W.B.; White, F.F.; Yang, B. Broad-spectrum resistance to bacterial blight in rice using genome editing. Nat. Biotechnol.,  2019, 37(11), 1344-1350.
[http://dx.doi.org/10.1038/s41587-019-0267-z] [PMID:  31659337] 
[87] 
Ortigosa, A.; Gimenez-Ibanez, S.; Leonhardt, N.; Solano, R. Design of a bacterial speck resistant tomato by CRISPR/Cas9-mediated editing of SlJAZ2. Plant Biotechnol. J.,  2019, 17(3), 665-673.
[http://dx.doi.org/10.1111/pbi.13006] [PMID:  30183125] 
[88] 
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,  2016, 533(7603), 420-424.
[http://dx.doi.org/10.1038/nature17946] [PMID:  27096365] 
[89] 
Rees, H.A.; Liu, D.R. Base editing: Precision chemistry on the genome and transcriptome of living cells. Nat. Rev. Genet.,  2018, 19(12), 770-788.
[http://dx.doi.org/10.1038/s41576-018-0068-0] [PMID:  30341440] 
[90] 
Okuzaki, A.; Shimizu, T.; Kaku, K.; Kawai, K.; Toriyama, K. A novel mutated acetolactate synthase gene conferring specific resistance to pyrimidinyl carboxy herbicides in rice. Plant Mol. Biol.,  2007, 64(1-2), 219-224.
[http://dx.doi.org/10.1007/s11103-007-9146-y] [PMID:  17334827] 
[91] 
Zhang, R.; Liu, J.; Chai, Z.; Chen, S.; Bai, Y.; Zong, Y.; Chen, K.; Li, J.; Jiang, L.; Gao, C. Generation of herbicide tolerance traits and a new selectable marker in wheat using base editing. Nat. Plants,  2019, 5(5), 480-485.
[http://dx.doi.org/10.1038/s41477-019-0405-0] [PMID:  30988404] 
[92] 
Shimatani, Z.; Kashojiya, S.; Takayama, M.; Terada, R.; Arazoe, T.; Ishii, H.; Teramura, H.; Yamamoto, T.; Komatsu, H.; Miura, K.; Ezura, H.; Nishida, K.; Ariizumi, T.; Kondo, A. Targeted base editing in rice and tomato using a CRISPR-Cas9 cytidine deaminase fusion. Nat. Biotechnol.,  2017, 35(5), 441-443.
[http://dx.doi.org/10.1038/nbt.3833] [PMID:  28346401] 
[93] 
Chen, Y.; Wang, Z.; Ni, H.; Xu, Y.; Chen, Q.; Jiang, L. CRISPR/Cas9-mediated base-editing system efficiently generates gain-of-function mutations in Arabidopsis. Sci. China Life Sci.,  2017, 60(5), 520-523.
[http://dx.doi.org/10.1007/s11427-017-9021-5] [PMID:  28303459] 
[94] 
Tian, S.; Jiang, L.; Cui, X.; Zhang, J.; Guo, S.; Li, M.; Zhang, H.; Ren, Y.; Gong, G.; Zong, M.; Liu, F.; Chen, Q.; Xu, Y. Engineering herbi-cide-resistant watermelon variety through CRISPR/Cas9-mediated base-editing. Plant Cell Rep.,  2018, 37(9), 1353-1356.
[http://dx.doi.org/10.1007/s00299-018-2299-0] [PMID:  29797048] 
[95] 
Li, C.; Zong, Y.; Wang, Y.; Jin, S.; Zhang, D.; Song, Q.; Zhang, R.; Gao, C. Expanded base editing in rice and wheat using a Cas9-adenosine deaminase fusion. Genome Biol.,  2018, 19(1), 59.
[http://dx.doi.org/10.1186/s13059-018-1443-z] [PMID:  29807545] 
[96] 
Anzalone, A.V.; Randolph, P.B.; Davis, J.R.; Sousa, A.A.; Koblan, L.W.; Levy, J.M.; Chen, P.J.; Wilson, C.; Newby, G.A.; Raguram, A.; Liu, D.R. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature,  2019, 576(7785), 149-157.
[http://dx.doi.org/10.1038/s41586-019-1711-4] [PMID:  31634902] 
[97] 
Anzalone, A.V.; Koblan, L.W.; Liu, D.R. Genome editing with CRISPR-Cas nucleases, base editors, transposases and prime editors. Nat. Biotechnol.,  2020, 38(7), 824-844.
[http://dx.doi.org/10.1038/s41587-020-0561-9] [PMID:  32572269] 
[98] 
Hua, K.; Jiang, Y.; Tao, X.; Zhu, J.K. Precision genome engineering in rice using prime editing system. Plant Biotechnol. J.,  2020, 18(11), 2167-2169.
[http://dx.doi.org/10.1111/pbi.13395] [PMID:  32372479] 
[99] 
Lin, Q.; Zong, Y.; Xue, C.; Wang, S.; Jin, S.; Zhu, Z.; Wang, Y.; Anzalone, A.V.; Raguram, A.; Doman, J.L.; Liu, D.R.; Gao, C. Prime ge-nome editing in rice and wheat. Nat. Biotechnol.,  2020, 38(5), 582-585.
[http://dx.doi.org/10.1038/s41587-020-0455-x] [PMID:  32393904] 
[100] 
Tang, X.; Sretenovic, S.; Ren, Q.; Jia, X.; Li, M.; Fan, T.; Yin, D.; Xiang, S.; Guo, Y.; Liu, L.; Zheng, X.; Qi, Y.; Zhang, Y. Plant prime editors enable precise gene editing in rice cells. Mol. Plant,  2020, 13(5), 667-670.
[http://dx.doi.org/10.1016/j.molp.2020.03.010] [PMID:  32222487] 
[101] 
Xu, W.; Zhang, C.; Yang, Y.; Zhao, S.; Kang, G.; He, X.; Song, J.; Yang, J. Versatile nucleotides substitution in plant using an improved prime editing system. Mol. Plant,  2020, 13(5), 675-678.
[http://dx.doi.org/10.1016/j.molp.2020.03.012] [PMID:  32234340] 
[102] 
Jiang, Y.Y.; Chai, Y.P.; Lu, M.H.; Han, X.L.; Lin, Q.; Zhang, Y.; Zhang, Q.; Zhou, Y.; Wang, X.C.; Gao, C.; Chen, Q.J. Prime editing effi-ciently generates W542L and S621I double mutations in two ALS genes in maize. Genome Biol.,  2020, 21(1), 257.
[http://dx.doi.org/10.1186/s13059-020-02170-5] [PMID:  33023639] 
[103] 
Florian Veillet, M-P.K.; Chauvin, L.; Guyon-Debast, A.; Chauvin, J-E.; Gallois, J-L.; Nogué, F. Prime editing is achievable in the tetra-ploid potato, but needs improvement. bioRxiv, 2020.
[104] 
Butt, H.; Rao, G.S.; Sedeek, K.; Aman, R.; Kamel, R.; Mahfouz, M. Engineering herbicide resistance via prime editing in rice. Plant Biotechnol. J.,  2020, 18(12), 2370-2372.
[http://dx.doi.org/10.1111/pbi.13399] [PMID:  32415890] 
[105] 
Buell, C.R.; Voytas, D. Technology turbocharges functional genomics. Plant Cell,  2017, 29(6), 1179-1180.
[http://dx.doi.org/10.1105/tpc.17.00443] [PMID:  28584164] 
[106] 
Shalem, O.; Sanjana, N.E.; Zhang, F. High-throughput functional genomics using CRISPR-Cas9. Nat. Rev. Genet.,  2015, 16(5), 299-311.
[http://dx.doi.org/10.1038/nrg3899] [PMID:  25854182] 
[107] 
Jacobs, T.B.; Zhang, N.; Patel, D.; Martin, G.B. Generation of a collection of mutant tomato lines using pooled CRISPR libraries. Plant Physiol.,  2017, 174(4), 2023-2037.
[http://dx.doi.org/10.1104/pp.17.00489] [PMID:  28646085] 
[108] 
Lu, Y.; Ye, X.; Guo, R.; Huang, J.; Wang, W.; Tang, J.; Tan, L.; Zhu, J.K.; Chu, C.; Qian, Y. Genome-wide targeted mutagenesis in rice using the CRISPR/Cas9 system. Mol. Plant,  2017, 10(9), 1242-1245.
[http://dx.doi.org/10.1016/j.molp.2017.06.007] [PMID:  28645638] 
[109] 
Meng, X.; Yu, H.; Zhang, Y.; Zhuang, F.; Song, X.; Gao, S.; Gao, C.; Li, J. Construction of a genome-wide mutant library in rice using CRISPR/Cas9. Mol. Plant,  2017, 10(9), 1238-1241.
[http://dx.doi.org/10.1016/j.molp.2017.06.006] [PMID:  28645639] 
[110] 
Ford, K.; McDonald, D.; Mali, P. Functional genomics via CRISPR-cas. J. Mol. Biol.,  2019, 431(1), 48-65.
[http://dx.doi.org/10.1016/j.jmb.2018.06.034] [PMID:  29959923] 
[111] 
Bai, M.; Yuan, J.; Kuang, H.; Gong, P.; Li, S.; Zhang, Z.; Liu, B.; Sun, J.; Yang, M.; Yang, L.; Wang, D.; Song, S.; Guan, Y. Generation of a multiplex mutagenesis population via pooled CRISPR-Cas9 in soya bean. Plant Biotechnol. J.,  2020, 18(3), 721-731.
[http://dx.doi.org/10.1111/pbi.13239] [PMID:  31452351] 
[112] 
Liu, H.J.; Jian, L.; Xu, J.; Zhang, Q.; Zhang, M.; Jin, M.; Peng, Y.; Yan, J.; Han, B.; Liu, J.; Gao, F.; Liu, X.; Huang, L.; Wei, W.; Ding, Y.; Yang, X.; Li, Z.; Zhang, M.; Sun, J.; Bai, M.; Song, W.; Chen, H.; Sun, X.; Li, W.; Lu, Y.; Liu, Y.; Zhao, J.; Qian, Y.; Jackson, D.; Fernie, A.R.; Yan, J. High-throughput CRISPR/Cas9 mutagenesis streamlines trait gene identification in maize. Plant Cell,  2020, 32(5), 1397-1413.
[http://dx.doi.org/10.1105/tpc.19.00934] [PMID:  32102844] 
[113] 
Conko, G.; Kershen, D.L.; Miller, H.; Parrott, W.A. A risk-based approach to the regulation of genetically engineered organisms. Nat. Biotechnol.,  2016, 34(5), 493-503.
[http://dx.doi.org/10.1038/nbt.3568] [PMID:  27153279] 
[114] 
Hartung, F.; Schiemann, J. Precise plant breeding using new genome editing techniques: Opportunities, safety and regulation in the EU. Plant J.,  2014, 78(5), 742-752.
[http://dx.doi.org/10.1111/tpj.12413] [PMID:  24330272] 
[115] 
Ishii, T.; Araki, M. Consumer acceptance of food crops developed by genome editing. Plant Cell Rep.,  2016, 35(7), 1507-1518.
[http://dx.doi.org/10.1007/s00299-016-1974-2] [PMID:  27038939] 
[116] 
Jones, H.D. Regulatory uncertainty over genome editing. Nat. Plants,  2015, 1(1), 14011.
[http://dx.doi.org/10.1038/nplants.2014.11] [PMID:  27246057] 
[117] 
Schaart, J.G.; van de Wiel, C.C.M.; Lotz, L.A.P.; Smulders, M.J.M. Opportunities for products of new plant breeding techniques. Trends Plant Sci.,  2016, 21(5), 438-449.
[http://dx.doi.org/10.1016/j.tplants.2015.11.006] [PMID:  26654659] 
[118] 
Sprink, T.; Eriksson, D.; Schiemann, J.; Hartung, F. Regulatory hurdles for genome editing: Process- vs. product-based approaches in different regulatory contexts. Plant Cell Rep.,  2016, 35(7), 1493-1506.
[http://dx.doi.org/10.1007/s00299-016-1990-2] [PMID:  27142995] 
[119] 
Voytas, D.F.; Gao, C. Precision genome engineering and agriculture: Opportunities and regulatory challenges. PLoS Biol.,  2014, 12(6), e1001877.
[http://dx.doi.org/10.1371/journal.pbio.1001877] [PMID:  24915127] 
[120] 
Friedrichs, S.T.Y.; Kearns, P.; Dagallier, B.; Oshima, R.; Schofield, J.; Moreddu, C. An overview of regulatory approaches to genome edit-ing in agriculture. Biotechnol. Res. Innov.,  2019, 3(2), 208-220.
[http://dx.doi.org/10.1016/j.biori.2019.07.001] 
[121] 
 Global gene editing regulation tracker. Available from: https://crispr-gene-editing-regs-tracker.geneticliteracyproject.org/
[122] 
 Environment, A. C. o. R. t. t. Genetically modified organisms: New plant growing methods. Available from: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/239542/new-techniques-used-in-plant-breeding.pdf
[123] 
Menz, J.; Modrzejewski, D.; Hartung, F.; Wilhelm, R.; Sprink, T. Genome edited crops touch the market: A view on the global develop-ment and regulatory environment. Front Plant Sci.,  2020, 11, 586027.
[http://dx.doi.org/10.3389/fpls.2020.586027] 
[124] 
Nejat, N.; Mantri, N. Plant immune system: Crosstalk between responses to biotic and abiotic stresses the missing link in understanding plant defence. Curr. Issues Mol. Biol.,  2017, 23, 1-16.
[PMID:  28154243] 
[125] 
Gan, X.; Stegle, O.; Behr, J.; Steffen, J.G.; Drewe, P.; Hildebrand, K.L.; Lyngsoe, R.; Schultheiss, S.J.; Osborne, E.J.; Sreedharan, V.T.; Kahles, A.; Bohnert, R.; Jean, G.; Derwent, P.; Kersey, P.; Belfield, E.J.; Harberd, N.P.; Kemen, E.; Toomajian, C.; Kover, P.X.; Clark, R.M.; Rätsch, G.; Mott, R. Multiple reference genomes and transcriptomes for Arabidopsis thaliana. Nature,  2011, 477(7365), 419-423.
[http://dx.doi.org/10.1038/nature10414] [PMID:  21874022] 
[126] 
Golicz, A.A.; Bayer, P.E.; Barker, G.C.; Edger, P.P.; Kim, H.; Martinez, P.A.; Chan, C.K.K.; Severn-Ellis, A.; McCombie, W.R.; Parkin, I.A.P.; Paterson, A.H.; Pires, J.C.; Sharpe, A.G.; Tang, H.; Teakle, G.R.; Town, C.D.; Batley, J.; Edwards, D. The pangenome of an agro-nomically important crop plant Brassica oleracea. Nat. Commun.,  2016, 7(1), 13390.
[http://dx.doi.org/10.1038/ncomms13390] [PMID:  27834372] 
[127] 
Montenegro, J.D.; Golicz, A.A.; Bayer, P.E.; Hurgobin, B.; Lee, H.; Chan, C.K.K.; Visendi, P.; Lai, K.; Doležel, J.; Batley, J.; Edwards, D. The pangenome of hexaploid bread wheat. Plant J.,  2017, 90(5), 1007-1013.
[http://dx.doi.org/10.1111/tpj.13515] [PMID:  28231383] 
[128] 
Zhao, Q.; Feng, Q.; Lu, H.; Li, Y.; Wang, A.; Tian, Q.; Zhan, Q.; Lu, Y.; Zhang, L.; Huang, T.; Wang, Y.; Fan, D.; Zhao, Y.; Wang, Z.; Zhou, C.; Chen, J.; Zhu, C.; Li, W.; Weng, Q.; Xu, Q.; Wang, Z.X.; Wei, X.; Han, B.; Huang, X. Pan-genome analysis highlights the extent of genomic variation in cultivated and wild rice. Nat. Genet.,  2018, 50(2), 278-284.
[http://dx.doi.org/10.1038/s41588-018-0041-z] [PMID:  29335547] 
[129] 
Yu, J.; Golicz, A.A.; Lu, K.; Dossa, K.; Zhang, Y.; Chen, J.; Wang, L.; You, J.; Fan, D.; Edwards, D.; Zhang, X. Insight into the evolution and functional characteristics of the pan-genome assembly from sesame landraces and modern cultivars. Plant Biotechnol. J.,  2019, 17(5), 881-892.
[http://dx.doi.org/10.1111/pbi.13022] [PMID:  30315621] 
[130] 
Gao, L.; Gonda, I.; Sun, H.; Ma, Q.; Bao, K.; Tieman, D.M.; Burzynski-Chang, E.A.; Fish, T.L.; Stromberg, K.A.; Sacks, G.L.; Thannhauser, T.W.; Foolad, M.R.; Diez, M.J.; Blanca, J.; Canizares, J.; Xu, Y.; van der Knaap, E.; Huang, S.; Klee, H.J.; Giovannoni, J.J.; Fei, Z. The tomato pan-genome uncovers new genes and a rare allele regulating fruit flavor. Nat. Genet.,  2019, 51(6), 1044-1051.
[http://dx.doi.org/10.1038/s41588-019-0410-2] [PMID:  31086351] 
[131] 
Jayakodi, M.; Padmarasu, S.; Haberer, G.; Bonthala, V.S.; Gundlach, H.; Monat, C.; Lux, T.; Kamal, N.; Lang, D.; Himmelbach, A.; Ens, J.; Zhang, X.Q.; Angessa, T.T.; Zhou, G.; Tan, C.; Hill, C.; Wang, P.; Schreiber, M.; Boston, L.B.; Plott, C.; Jenkins, J.; Guo, Y.; Fiebig, A.; Budak, H.; Xu, D.; Zhang, J.; Wang, C.; Grimwood, J.; Schmutz, J.; Guo, G.; Zhang, G.; Mochida, K.; Hirayama, T.; Sato, K.; Chalmers, K.J.; Langridge, P.; Waugh, R.; Pozniak, C.J.; Scholz, U.; Mayer, K.F.X.; Spannagl, M.; Li, C.; Mascher, M.; Stein, N. The barley pan-genome reveals the hidden legacy of mutation breeding. Nature,  2020, 588(7837), 284-289.
[http://dx.doi.org/10.1038/s41586-020-2947-8] [PMID:  33239781] 
[132] 
Hwang, H.H.; Yu, M.; Lai, E.M. Agrobacterium-mediated plant transformation: Biology and applications. Arabidopsis Book,  2017, 15, e0186.
[http://dx.doi.org/10.1199/tab.0186] [PMID:  31068763] 
[133] 
Mao, Y.; Botella, J.R.; Liu, Y.; Zhu, J.K. Gene editing in plants: Progress and challenges. Natl. Sci. Rev.,  2019, 6(3), 421-437.
[http://dx.doi.org/10.1093/nsr/nwz005] [PMID:  34691892] 
[134] 
Kelliher, T.; Starr, D.; Su, X.; Tang, G.; Chen, Z.; Carter, J.; Wittich, P.E.; Dong, S.; Green, J.; Burch, E.; McCuiston, J.; Gu, W.; Sun, Y.; Strebe, T.; Roberts, J.; Bate, N.J.; Que, Q. One-step genome editing of elite crop germplasm during haploid induction. Nat. Biotechnol.,  2019, 37(3), 287-292.
[http://dx.doi.org/10.1038/s41587-019-0038-x] [PMID:  30833776] 
[135] 
Maher, M.F.; Nasti, R.A.; Vollbrecht, M.; Starker, C.G.; Clark, M.D.; Voytas, D.F. Plant gene editing through de novo induction of meri-stems. Nat. Biotechnol.,  2020, 38(1), 84-89.
[http://dx.doi.org/10.1038/s41587-019-0337-2] [PMID:  31844292] 
[136] 
Ran, Y.; Liang, Z.; Gao, C. Current and future editing reagent delivery systems for plant genome editing. Sci. China Life Sci.,  2017, 60(5), 490-505.
[http://dx.doi.org/10.1007/s11427-017-9022-1] [PMID:  28527114] 
[137] 
Lowe, K.; Wu, E.; Wang, N.; Hoerster, G.; Hastings, C.; Cho, M.J.; Scelonge, C.; Lenderts, B.; Chamberlin, M.; Cushatt, J.; Wang, L.; Ryan, L.; Khan, T.; Chow-Yiu, J.; Hua, W.; Yu, M.; Banh, J.; Bao, Z.; Brink, K.; Igo, E.; Rudrappa, B.; Shamseer, P.M.; Bruce, W.; Newman, L.; Shen, B.; Zheng, P.; Bidney, D.; Falco, C.; Register, J.; Zhao, Z.Y.; Xu, D.; Jones, T.; Gordon-Kamm, W. Morphogenic regulators Baby boom and Wuschel improve monocot transformation. Plant Cell,  2016, 28(9), 1998-2015.
[http://dx.doi.org/10.1105/tpc.16.00124] [PMID:  27600536] 
[138] 
Lowe, K.; La Rota, M.; Hoerster, G.; Hastings, C.; Wang, N.; Chamberlin, M.; Wu, E.; Jones, T.; Gordon-Kamm, W. Rapid genotype “in-dependent” Zea mays L. (maize) transformation via direct somatic embryogenesis. In Vitro Cell. Dev. Biol. Plant,  2018, 54(3), 240-252.
[http://dx.doi.org/10.1007/s11627-018-9905-2] [PMID:  29780216] 
[139] 
Mookkan, M.; Nelson-Vasilchik, K.; Hague, J.; Zhang, Z.J.; Kausch, A.P. Selectable marker independent transformation of recalcitrant maize inbred B73 and sorghum P898012 mediated by morphogenic regulators BABY BOOM and WUSCHEL2. Plant Cell Rep.,  2017, 36(9), 1477-1491.
[http://dx.doi.org/10.1007/s00299-017-2169-1] [PMID:  28681159] 
[140] 
LeBlanc, C.; Zhang, F.; Mendez, J.; Lozano, Y.; Chatpar, K.; Irish, V.F.; Jacob, Y. Increased efficiency of targeted mutagenesis by CRISPR/Cas9 in plants using heat stress. Plant J.,  2018, 93(2), 377-386.
[http://dx.doi.org/10.1111/tpj.13782] [PMID:  29161464] 
[141] 
Nandy, S.P.; Zhao, S.; Srivastava, V. Heat-shock-inducible CRISPR/Cas9 system generates heritable mutations in rice. Plant Direct,  2019, 3(5), 1-14.
[142] 
Barone, P.; Wu, E.; Lenderts, B.; Anand, A.; Gordon-Kamm, W.; Svitashev, S.; Kumar, S. Efficient gene targeting in maize using inducible CRISPR-Cas9 and marker-free donor template. Mol. Plant,  2020, 13(8), 1219-1227.
[http://dx.doi.org/10.1016/j.molp.2020.06.008] [PMID:  32574856] 
[143] 
Chapman, J.E.G.; Gillum, D.; Kiani, S. Approaches to reduce CRISPR off-target effects for safer genome editing. Appl. Biosaf.,  2017, 22(1), 7-13.
[http://dx.doi.org/10.1177/1535676017694148] 
[144] 
Naeem, M.; Majeed, S.; Hoque, M.Z.; Ahmad, I. Latest developed strategies to minimize the off-target effects in CRISPR-Cas-mediated genome editing. Cells-Basel,  2020, 9(7), 1608.
[145] 
Coelho, M.A.; De Braekeleer, E.; Firth, M.; Bista, M.; Lukasiak, S.; Cuomo, M.E.; Taylor, B.J.M. CRISPR GUARD protects off-target sites from Cas9 nuclease activity using short guide RNAs. Nat. Commun.,  2020, 11(1), 4132.
[http://dx.doi.org/10.1038/s41467-020-17952-5] [PMID:  32807781] 
[146] 
Lin, Q.; Jin, S.; Zong, Y.; Yu, H.; Zhu, Z.; Liu, G.; Kou, L.; Wang, Y.; Qiu, J.L.; Li, J.; Gao, C. High-efficiency prime editing with opti-mized, paired pegRNAs in plants. Nat. Biotechnol.,  2021, 39(8), 923-927.
[http://dx.doi.org/10.1038/s41587-021-00868-w] [PMID:  33767395] 
[147] 
Hassan, M.M.; Yuan, G.; Chen, J-G.; Tuskan, G.A.; Yang, X. Prime editing technology and its prospects for future applications in plant biology research; Bio. Design Res, 2020, p. 9350905.
[148] 
Li, Z.; Zhang, D.; Xiong, X.; Yan, B.; Xie, W.; Sheen, J.; Li, J.F. A potent Cas9-derived gene activator for plant and mammalian cells. Nat. Plants,  2017, 3(12), 930-936.
[http://dx.doi.org/10.1038/s41477-017-0046-0] [PMID:  29158545] 
[149] 
Beying, N.; Schmidt, C.; Pacher, M.; Houben, A.; Puchta, H. CRISPR-Cas9-mediated induction of heritable chromosomal translocations in Arabidopsis. Nat. Plants,  2020, 6(6), 638-645.
[http://dx.doi.org/10.1038/s41477-020-0663-x] [PMID:  32451449] 
[150] 
Schmidt, C.; Fransz, P.; Rönspies, M.; Dreissig, S.; Fuchs, J.; Heckmann, S.; Houben, A.; Puchta, H. Changing local recombination patterns in Arabidopsis by CRISPR/Cas mediated chromosome engineering. Nat. Commun.,  2020, 11(1), 4418.
[http://dx.doi.org/10.1038/s41467-020-18277-z] [PMID:  32887885] 
[151] 
Østerberg, J.T.; Xiang, W.; Olsen, L.I.; Edenbrandt, A.K.; Vedel, S.E.; Christiansen, A.; Landes, X.; Andersen, M.M.; Pagh, P.; Sandøe, P.; Nielsen, J.; Christensen, S.B.; Thorsen, B.J.; Kappel, K.; Gamborg, C.; Palmgren, M. Accelerating the domestication of new crops: Feasibil-ity and approaches. Trends Plant Sci.,  2017, 22(5), 373-384.
[http://dx.doi.org/10.1016/j.tplants.2017.01.004] [PMID:  28262427] 
[152] 
Li, T.; Yang, X.; Yu, Y.; Si, X.; Zhai, X.; Zhang, H.; Dong, W.; Gao, C.; Xu, C. Domestication of wild tomato is accelerated by genome editing. Nat. Biotechnol.,  2018, 36(12), 1160-1163.
[http://dx.doi.org/10.1038/nbt.4273] [PMID:  30272676] 
[153] 
Zsögön, A.; Čermák, T.; Naves, E.R.; Notini, M.M.; Edel, K.H.; Weinl, S.; Freschi, L.; Voytas, D.F.; Kudla, J.; Peres, L.E.P. De novo do-mestication of wild tomato using genome editing. Nat. Biotechnol.,  2018, 36(12), 1211-1216.
[http://dx.doi.org/10.1038/nbt.4272] [PMID:  30272678] 
[154] 
Nicolia, A.; Manzo, A.; Veronesi, F.; Rosellini, D. An overview of the last 10 years of genetically engineered crop safety research. Crit. Rev. Biotechnol.,  2014, 34(1), 77-88.
[http://dx.doi.org/10.3109/07388551.2013.823595] [PMID:  24041244] 
[155] 
Zaidi, S.S.E.A.; Vanderschuren, H.; Qaim, M.; Mahfouz, M.M.; Kohli, A.; Mansoor, S.; Tester, M. New plant breeding technologies for food security. Science,  2019, 363(6434), 1390-1391.
[http://dx.doi.org/10.1126/science.aav6316] [PMID:  30923209] 
[156] 
He, T.H.; Li, C.D. Harness the power of genomic selection and the potential of germplasm in crop breeding for global food security in the era with rapid climate change. Crop J.,  2020, 8(5), 688-700.
[http://dx.doi.org/10.1016/j.cj.2020.04.005] 
Cite As
Current Chinese Science

Swiftly Evolving CRISPR Genome Editing: A Revolution in Genetic Engineering for Developing Stress-Resilient Crops

Abstract

Graphical Abstract
