The End of the GMO?
Introduction: The End of the GMO?
There is no robust and parsimonious explanation for differences in diffusion of agricultural biotechnology across countries or across time. Variables that delineate common political rifts in international trade and politics fail to explain variation. The one constant is a risk-utility balance, filtered through structures of regulatory mechanisms and their associated political ecology: Agriculture vs Environment ministries, eg. This paper assesses in a preliminary way political prospects of new technologies for genetic engineering of agricultural plants, especially CRISPR-Cas9. The frontiers of plant breeding are moving away from transgenesis as dominant form of plant breeding and test of what requires special regulation -- a 'GMO' or 'LMO.' New regulatory constructs treat gene-edited plants more as mutagenized crops -- in a targeted rather than random way. Since the thousands of mutagenized agricultural plants have been immune to regulation as ‘GMOs’ – and can be ‘organic’ - this political battle for definition will shape the future diffusion of agricultural – and other – biotechnologies globally, marking the end of pointless battles over the ‘GMO.’ Because of the utility of new techniques for consumers and farmers alike – unlike transgenic plants for the most part – as well as for the environment and human health, the risk-utility balance is being fundamentally altered.
This past summer, possibly the world’s first meal consisting of genome-edited (CRISPR) foods was served up in Sweden by scientist Stefan Jannson (Zhang et al., 2016). The meal — ‘Tagliatelle with CRISPRy fried vegetables’ — was served with cabbage grown directly on Umeå University’s campus. The Swedish Board of Agriculture ruled that CRISPR-Cas genome-edited crops do not fall under the EU’s definition of a genetically modified organism (GMO); no special regulation was necessary. Similar rulings have occurred in the U.S. and Canada. If this trend continues, can we expect to see many more meals based on genome-edited crops across Europe and elsewhere in the future? This new and rapidly expanding form of technology, and impending public responses, will force a fundamental re-evaluation of how to regulate tomorrow’s food crops – and much else.
The genomics revolution that enabled modern agricultural biotechnology has been a source of optimism and controversy since its inception: suicide seeds and silver bullets. Social and political resistance has prevented adoption and diffusion in many countries, in law if not in farmer practice (Herring and Paarlberg, 2016). Innovations in crop genetic engineering have, where accepted, significantly increased the number and diversity of crop varieties and enhanced harvested yield, improved nutritional content and conferred resistance to biotic and physical stresses (Collinge et al., 2010; Deikman et al. 2012). Genomic techniques have proved valuable to complement conventional breeding methods. Genetically modified (GM) crops have also demonstrated potential to address malnutrition and to improve agronomic practices where other approaches fail: virus-resistance is a prominent example. Some biotech crops enable labor-saving strategies that allow farmers additional time for other activities. At the same time, labor displacement has not proved so detrimental to the rural poor as first hypothesized and there is even some evidence of potential for decreasing gender inequality under certain cropping conditions and village economy (Katage and Qaim 2012; Kouser et al., 2017). Crops with improved yield and improved resistance to pests, weeds and environmental stresses such as drought and flooding can assist farmers who lack access to public safety-net mechanisms or reliable markets. Resilience to certain environmental shocks that result from climate change is one possible outcome (Cominelli and Tonelli, 2010). While the first genetically modified crops were bred for improved agronomic traits, agricultural biotechnology has pursued as well crops with improved human health benefits (Bhutta et al., 2013).
As often in new technology, promises of potential have freqently outrun workable options on the ground for farmers. That situation may be changing dramatically. Over the past few years, a new technology known as genome editing has come to the forefront. Genome editing systems based on existing bacterial defense and repair pathways within cells are being developed with applications in crop science, livestock improvement and medicine (Montenegro, 2016). In general, the technology is rapid, precise and efficient, compared to other means of developing desired characteristics in plants: transgenesis, chemical or radiation-induced mutagenesis and conventional breeding. These attributes, coupled with relatively low cost and comparative freedom from regulatory encumbrances, have enabled genome editing to revolutionize basic molecular-biology research and take it to an entirely new level.
Genome editing systems based on clustered regularly interspaced short palindrome repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), for example, are now available in most research labs and exhibit forms of utility ranging from those as small as examining the function of a particular gene fragment to as large as the genome-wide mutagenesis screening of an entire crop for novel traits (Ding et al., 2016, Bortesi and Fischer, 2015, Sauer et al., 2016). Furthermore, genome editing provides a plethora of applications in the crop sciences. Unlike transgenic plants, genome editing allows plant breeders to know exactly where a change has been made in the genome, leaves no trace of that process, and enables all copies of a particular gene to be altered within a plant at the same time. Moreover, crop genome editing shows signs of proving more socially acceptable than GMOs – and thus subject to fewer regulatory barriers, though large ethical issues and property questions remain to be settled (Potrykus, 2010, Perez-Massof et al., 2013).
The following review illustrates how genome editing fits into the broader frame of agricultural development. It describes how genome editing differs from and builds upon earlier achievements in genomics. Next, it provides examples of how genome editing is being applied today to improve traits for the world’s major food crops. The use of ‘gene drive’ as a mechanism to spread newly edited genomes rapidly, as well as examples of the use of genome editing for livestock improvement and for medical breakthroughs in human health are provided. The review ends with a discourse regarding the future of genome editing as a tool to address some of humanity’s greatest challenges, and, reciprocally, some social, economic and ethical questions requiring coordinated responses to move forward.
Alton E.W., Boyd A.C., Davies J.C., Gill D.R., Griesenbach U., Harrison P.T., Henig N., Higgins T., Hyde S.C., Innes J.A., Korman M.S. Genetic medicines for CF: Hype versus reality. Pediatr Pulmonol. 2016 Oct;51(S44):S5-S17.
Aswath, C.R., Krisnaraj, P.U., Padmanaban, G. Why India Needs biotechnology to ensure food and nutrition security. Genetically Modified Organisms in Food, 1st Edition Production, Safety, Regulation and Public Health, 2016, Elsevier.
Barabaschi D, Tondelli A, Desiderio F, Volante A, Vaccino P, Valè G, Cattivelli L. Next generation breeding. Plant Sci. 2016 Jan;242:3-13.
Barakate A, Stephens J. An Overview of CRISPR-Based Tools and Their Improvements: New Opportunities in Understanding Plant-Pathogen Interactions for Better Crop Protection. Front Plant Sci. 2016 Jun 1;7:765.
Bazuin, S., Azadi, H., Witlox, F. Application of GM crops in Sub-Saharan Africa: lessons learned from Green Revolution. Biotechnol Adv., 2011, Nov-Dec;29(6), 908-12.
Benston S. CRISPR, a Crossroads in Genetic Intervention: Pitting the Right to Health against the Right to Disability. Laws. 2016 Mar;5(1). pii: 5. Epub 2016 Feb 18.
Beyer P. Golden Rice and ‘Golden’ crops for human nutrition. N Biotechnol. 2010 Nov 30;27(5), 478-81.
Blanvillain-Baufumé S, Reschke M, Solé M, Auguy F, Doucoure H, Szurek B, Meynard D, Portefaix M, Cunnac S, Guiderdoni E, Boch J, Koebnik R. Targeted promoter editing for rice resistance to Xanthomonas oryzae pv. oryzae reveals differential activities for SWEET14-inducing TAL effectors. Plant Biotechnol J. 2016 Aug 19.
Bortesi L, Fischer R. The CRISPR/Cas9 system for plant genome editing and beyond. Biotechnol Adv. 2015 Jan-Feb;33(1):41-52.
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 Nov;166(3):1292-7. doi: 10.1104/pp.114.247577. Epub 2014 Sep 15.
Callaway E 2017 Gene drives thwarted by emergence of resistant organisms. Nature News. 31 January 2017
Cardi T, Neal Stewart C Jr. Progress of targeted genome modification approaches in higher plants. Plant Cell Rep. 2016 Jul;35(7):1401-16.
Char SN, Neelakandan AK, Nahampun H, Frame B, Main M, Spalding MH, Becraft PW, Meyers BC, Walbot V, Wang K, Yang B. An Agrobacterium-delivered CRISPR/Cas9 system for high-frequency targeted mutagenesis in maize. Plant Biotechnol J. 2016 Aug 11.
Evanega S and and M Lynas. 2015. Dialectic of the Pro-Poor Papaya. In Ronald J. Herring, ed. The Oxford Handbook of Food, Politics, and Society. New York and Oxford. 2015
FAO 2013, The State of Food Insecurity in the World, Executive Summary.
Garry, M.G. and Garry, M.G. Humanized organ generating animals. Regenerative Medicine 2016 11(7): 617-9.
Global Nutrition Report, Actions and Accountability to Accelerate the World’s Progress on Nutrition International Food Policy Research Institute, Issue Brief 82, November 2014.
Gonsalves D. Control of papaya ringspot virus in papaya: a case study. Annu Rev Phytopathol. 1998;36:415-37.
PMID: 28072792 DOI: 10.1038/nbt.3756
Galzi R, Kyrou K, Simoni A, Siniscalchi C, Katsanos D, Gribble M, Baker D, Marois E, Russell S, Burt A, Windbichler N, Crisanti A, Nolan T. A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nat Biotechnol. 2016 Jan;34(1):78-83.
Harriss, J. and D. Stewart. Science, Politics and the Framing of Modern Agricultural Technologies. In Herring, R. 2015. Oxford Handbook of Food, Politics and Society. Oxford University Press. Oxford and New York.
Hefferon, K.L. and R. J. Herring. In Press. The End of the GMO? Genome Editing, Gene Drives and New Frontiers of Plant Technology. Review of Agrarian Studies.
Herring, R. J. Stealth Seeds: Biosafety, Bioproperty, Biopolitics. Journal of Development Studies. Vol 43 No 1. 2007.
Herring, R. and M. Kandlikar. 2009. “Illicit Seeds: Intellectual Property and the Underground Proliferation of Agricultural Biotechnologies,” In S. Haunss and K. C. Shadlen (Eds). ‘The Politics of Intellectual Property: Contestation over the Ownership, Use, and Control of Knowledge and Information’. Cheltenham, UK: Edward Elgar, 56-79.
Herring, R. and R. Paarlberg, 2016. “The Political Economy of Biotechnology.” Annual
Review of Resource Economics. 8: 397-416 Annual Reviews. Palo Alto, CA. 2016.
Huang, S., Weigel, O., Beachy, R and Li, J. A proposed regulatory framework for genome-edited crops. 2016. Nature Genetics 48: 109-111.
Im W, Moon J, Kim M. Applications of CRISPR/Cas9 for Gene Editing in Hereditary Movement Disorders. J Mov Disord. 2016 Sep;9(3):136-43.
International Food Policy Research Institute, 2014, Global Hunger Index
ISAAA Brief 46 Executive Summary Global Status of Commercialized Biotech/GM Crops: 2013, Clive James. The International Service for the Acquisition of Agri-biotech Applications.
Zhang, S. CRISPR could usher in a new era of delicious GMO foods. 2016. The Atlantic, Sept. 19.
Jenko J, Gorjanc G, Cleveland MA, Varshney RK, Whitelaw CB, Woolliams JA, Hickey JM.Potential of promotion of alleles by genome editing to improve quantitative traits in livestock breeding programs. Genet Sel Evol. 2015 Jul 2;47:55.
Jia H, Orbovic V, Jones JB, Wang N. Modification of the PthA4 effector binding elements in Type I CsLOB1 promoter using Cas9/sgRNA to produce transgenic Duncan grapefruit alleviating XccΔpthA4:dCsLOB1.3 infection.Plant Biotechnol J. 2016 May;14(5):1291-301
Jia H, Wang N. Targeted genome editing of sweet orange using Cas9/sgRNA. PLoS One. 2014 Apr 7;9(4):e93806.
Johnson, N. 2015. It is practically impossible to define ‘GMOs.’ Grist. http://grist.org/food/mind-bomb-its-practically-impossible-to-define-gmos/
Jones, H.D. Future of breeding by genome editing is in the hands of regulators. GM Crops Food. 2015 6(4); 223-32.
Kathage J, Qaim M. 2012. Economic impacts and impact dynamics of Bt (Bacillus thuringiensis) cotton in India. PNAS 109(29):11652–56
Kim H, Kim ST, Ryu J, Choi MK, Kweon J, Kang BC, Ahn HM, Bae S, Kim J, Kim JS, Kim SG. A simple, flexible and high-throughput cloning system for plant genome editing via CRISPR-Cas system. J Integr Plant Biol. 2016 Aug;58(8):705-12.
Kolady, D. and Herring, R. Regulation of Genetically Engineered Crops in India: Implications of Uncertainty for Social Welfare, Competition and Innovation. Canadian Journal of Agricultural Economics. Vol 62 Issue 4. 2014. pp 471-490.
Kouser, S., Abedullah, Qalm, M. Bt cotton and employment effects for female agricultural laborers in Pakistan. New Biotechnology 2017 Jan; 34: 40-46.
Kumar S, Chandra A, Pandey KC. Bacillus thuringiensis (Bt) transgenic crop: an environment friendly insect-pest management strategy. J Environ Biol. 2008 Sep;29(5):641-53.
Kuntz M. Scientists Should Oppose the Drive of Postmodern Ideology. Trends Biotechnol. 2016 Sep 13. pii: S0167-7799(16)30146-9.
Kyndt T. et al, 2015 The genome of cultivated sweet potato contains Agrobacterium T-DNAs with expressed genes: An example of a naturally transgenic food crop. PNAS. http://www.pnas.org/content/112/18/5844.full
Lambert AR, Hallinan JP, Shen BW, Chik JK, Bolduc JM, Kulshina N, Robins LI, Kaiser BK, Jarjour J, Havens K, Scharenberg AM, Stoddard BL. Indirect DNA Sequence Recognition and Its Impact on Nuclease Cleavage Activity. Structure. 2016 Jun 7;24(6):862-73.
Languin, K. Genetic engineering to the rescue against invasive species? National Geographic, July 18, 2014.
Ledford, H. Why the CRISPR patent verdict isn’t the end of the story. Nature February 17, 2017. doi:10.1038/nature.2017.21510
Ledford, H. Gene-editing surges as US rethinks regulations. Nature, 2016 532: 158-9.
Li J, Meng X, Zong Y, Chen K, Zhang H, Liu J, Li J, Gao C.
Nat Plants. 2016a Sep 12;2:16139.
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. 2016b Mar 30;7:377.
Liang, P., Xu, Y., Zhang, X. et al. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes Protein Cell (2015) 6: 363. doi:10.1007/s13238-015-0153-5
Lillico SG, Proudfoot C, Carlson DF, Stverakova D, Neil C, Blain C, King TJ, Ritchie WA, Tan W, Mileham AJ, McLaren DG, Fahrenkrug SC, Whitelaw CB. Live pigs produced from genome edited zygotes. Sci Rep. 2013 Oct 10;3:2847.
Long SP, Marshall-Colon A, Zhu XG. Meeting the global food demand of the future by engineering crop photosynthesis and yield potential. Cell. 2015 Mar 26;161(1):56-66.
Mao Y, Botella JR, Zhu JK. Heritability of targeted gene modifications induced by plant-optimized CRISPR systems. Cell Mol Life Sci. 2016 Sep 27.
Merkert S, Martin U. Targeted genome engineering using designer nucleases: State of the art and practical guidance for application in human pluripotent stem cells. Stem Cell Res. 2016 Mar;16(2):377-86.
Montenegro, M. (2016) CRISPR is coming to agriculture — with big implications for food, farmers, consumers and nature. ENSIA http://ensia.com/voices/crispr-is-coming-to-agriculture-with-big-implications-for-food-farmers-consumers-and-nature/
National Academies Press, 2016 Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values. https://www.nap.edu/catalog/23405/gene-drives-on-the-horizon-advancing-science-navigating-uncertainty-and Aligning Research with Public Values
Nature Editorial. 2/22/2017. http://www.nature.com/news/gene-editing-in-legal-limbo-in-europe-1.21515
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 Feb 13;156(4):836-43.
Nuiten E. , M. M. Messmer, E. T. Lammerts van Bueren. 2017. Concepts and Strategies of Organic Plant Breeding in Light of Novel Breeding Techniques. Sustainability 2017, 9, 18; doi:10.3390/su9010018.
Ossola, A. 2016. CRISPR-modified corn may soon be ready for market. Popular Science September 6 Issue.
Paarlberg RL. 2001. The Politics of Precaution: Genetically Modified Crops in Developing Countries. Baltimore, MD: Johns Hopkins Univ. Press
Paarlberg RL. 2008. Starved for Science: Keeping Biotechnology Out of Africa. Cambridge: Harvard Univ. Press
Pan C, Ye L, Qin L, Liu X, He Y, Wang J, Chen L, Lu G.CRISPR/Cas9-mediated efficient and heritable targeted mutagenesis in tomato plants in the first and later generations. Sci Rep. 2016 Apr 21;6:24765.
Paul JW 3rd, Qi Y. CRISPR/Cas9 for plant genome editing: accomplishments, problems and prospects. Plant Cell Rep. 2016 Jul;35(7):1417-27.
Pérez-Massot, E., Banakar, R., Gómez-Galera, S., Zorrilla-López, U., Sanahuja, G., Arjó, G., Miralpeix, B., Vamvaka, E., Farré, G., Rivera, S.M., Dashevskaya, S., Berman, J., Sabalza, M., Yuan, D., Bai, C., Bassie, L., Twyman, R.M., Capell, T., Christou, P., Zhu, C. The contribution of transgenic plants to better health through improved nutrition: opportunities and constraints. Genes Nutr. 2013, Jan;8(1), 29-41.
Quétier F. The CRISPR-Cas9 technology: Closer to the ultimate toolkit for targeted genome editing. Plant Sci. 2016 Jan;242:65-76.
Regalado, A. CRISPR Gene Editing to Be Tested on People by 2017, Says Editas MIT Technology Review November 5, 2015.
Ricroch AE, Hénard-Damave MC. Next biotech plants: new traits, crops, developers and technologies for addressing global challenges. Crit Rev Biotechnol. 2016 Aug;36(4):675-90
Sander, J.D. Joung, J.K. CRISPR-Cas systems for editing, regulating and targeting genomes Nature Biotechnology 32, 347–355 (2014).
Sauer NJ, Mozoruk J, Miller RB, Warburg ZJ, Walker KA, Beetham PR, Schöpke CR, Gocal GF.Oligonucleotide-directed mutagenesis for precision gene editing. Plant Biotechnol J. 2016 Feb;14(2):496-502.
Saey, T.H. Gene drives spread their wings. Science News, 2015, Vol. 188, No. 12, p. 16.
Shantharam, S. Genome editing: the benefits and the ethics. Magazine July 15, 2016.
Shi J, Gao H, Wang H, Lafitte HR, Archibald RL, Yang M, Hakimi SM, Mo H, Habben JE. ARGOS8 variants generated by CRISPR-Cas9 improve maize grain yield under field drought stress conditions. Plant Biotechnol J. 2016 Jul 21.
Shukla VK, Doyon Y, Miller JC, DeKelver RC, Moehle EA, Worden SE, Mitchell JC, Arnold NL, Gopalan S, Meng X, Choi VM, Rock JM, Wu YY, Katibah GE, Zhifang G, McCaskill D, Simpson MA, Blakeslee B, Greenwalt SA, Butler HJ, Hinkley SJ, Zhang L, Rebar EJ, Gregory PD, Urnov FD. Precise genome modification in the crop species Zea mays using zinc-finger nucleases. Nature. 2009 May 21;459(7245):437-41.
Singh RP, Hodson DP, Jin Y, Lagudah ES, Ayliffe MA, Bhavani S, Rouse MN, Pretorius ZA, Szabo LJ, Huerta-Espino J, Basnet BR, Lan C, Hovmøller MS. Emergence and Spread of New Races of Wheat Stem Rust Fungus: Continued Threat to Food Security and Prospects of Genetic Control. Phytopathology. 2015 Jul;105(7):872-84
Stella S, Montoya G. The genome editing revolution: A CRISPR-Cas TALE off-target story. Bioessays. 2016 Jul;38 Suppl 1:S4-S13.
Stone D, Niyonzima N, Jerome KR. Genome editing and the next generation of antiviral therapy. infection. Hum Genet. 2016 Sep;135(9):1071-82.
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 Oct;169(2):931-45.
Talan, J. News from the Society for Neuroscience Annual Meeting: Gene Editing Techniques Show Promise in Silencing or Inhibiting the Mutant Huntington’s Disease Gene. Neurology Today: 19 November 2015 – Volume 15 – Issue 22 – p 14–16
Tan W, Carlson DF, Lancto CA, Garbe JR, Webster DA, Hackett PB, Fahrenkrug SC. Efficient nonmeiotic allele introgression in livestock using custom endonucleases. Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16526-31.
Unglesbee, E. 2016. Brave New Crops. Progressive Farmer, 1-2. October Issue.
Wang Y, Cheng X, Shan Q, Zhang Y, Liu J, Gao C, Qiu JL. Simultaneous editing of three homoeoalleles in hexaploid bread wheat confers heritable resistance to powdery mildew. Nat Biotechnol. 2014 Sep;32(9):947-51.
Wang F, Wang C, Liu P, Lei C, Hao W, Gao Y, Liu YG, Zhao K. Enhanced Rice Blast Resistance by CRISPR/Cas9-Targeted Mutagenesis of the ERF Transcription Factor Gene OsERF922. PLoS One. 2016 Apr 26;11(4):e0154027.
Wang F, Qi LS. Applications of CRISPR Genome Engineering in Cell Biology. Trends Cell Biol. 2016 Nov;26(11):875-888.
Wang M, Glass ZA, Xu Q. Non-viral delivery of genome-editing nucleases for gene therapy. Gene Ther. 2016 Oct 31.
Wieczorek, A. CRISPR-Cas9 and gene drives: the risks and benefits of game-changing technology Biotech In focus. Cooperative Extension Service, University of Hawaii at Manoa. July 2016, Issue 52.
Wolf, J.D., Wang, K., Yang, B. The regulatory status of genome-edited crops. Plant Biotechnology Journal 2016 14(2): 510-18.
Yao J, Huang J, Zhao J. Genome editing revolutionize the creation of genetically modified pigs for modeling human diseases. Hum Genet. 2016 Sep;135(9):1093-105.
Yee JK. Off-target effects of engineered nucleases. FEBS J. 2016 Sep;283(17):3239-48.
Yi L, Li J. CRISPR-Cas9 therapeutics in cancer: promising strategies and present challenges. Biochim Biophys Acta. 2016 Sep 15;1866(2):197-207.
Yin H, Xue W, Chen S, Bogorad RL, Benedetti E, Grompe M, Koteliansky V, Sharp PA, Jacks T, Anderson DG. Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nat Biotechnol. 2014 Jun;32(6):551-3. (hereditary tyrosinemia)
Zhang D, Li Z, Li JF. Targeted Gene Manipulation in Plants Using the CRISPR/Cas Technology. J Genet Genomics. 2016 May 20;43(5):251-62.
Zhao X, Ni W, Chen C, Sai W, Qiao J, Sheng J, Zhang H, Li G, Wang D, Hu S. Targeted Editing of Myostatin Gene in Sheep by Transcription Activator-like Effector Nucleases. Asian-Australas J Anim Sci. 2016 Mar;29(3):413-8.
Zhu C, Bortesi L, Baysal C, Twyman RM, Fischer R, Capell T, Schillberg S, Christou P. Characteristics of Genome Editing Mutations in Cereal Crops. Trends Plant Sci. 2016 Sep 16. pii: S1360-1385(16)30120-0.