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Genome Editing in Agriculture Number 60 Issue Paper July 2018 Genome Editing in Agriculture: Methods, Applications, and Governance A paper in the series on The Need for Agricultural Innovation to Sustainably Feed the World by 2050 The power of genome editing suggests that, if conducive social and regulatory conditions are in place, it can substan- tially increase the positive impacts of plant and animal breeding on human welfare and sustainability. (Shutterstock photos from Yaroslava [corn], vchal [gene manipulation], and Shyamalamuralinath [calf].) limitations of the approach. The paper decrease socioeconomic disparities, ABSTRACT also presents an overview of the current mitigate barriers to trade, and moderate Genome editing is the process of landscape of governance of genome edit- political and market dependencies), the making precise, targeted sequence ing, including existing regulations, inter- paper aims to provide a conceptual and changes in the deoxyribonucleic acid national agreements, and standards and knowledge-based foundation for regula- of living cells and organisms. Recent codes of conduct, as well as a discussion tory agencies, policy- and lawmakers, advances have made genome editing of factors that affect governance, includ- private and public research institutions, widely applicable, offering the opportu- ing comparison with other approaches to industry, and the general public. nity to rapidly advance basic and applied genetic modification, environmental and biology. In the face of the mounting animal welfare impacts of specific appli- food, fiber, feed, and fuel needs and the cations, values of producers and con- INTRODUCTION decreasing availability of land and water sumers, and economic impacts, among Twentieth-century advances in plant caused by global population growth, as others. Recognizing both that genome and animal breeding and agricultural well as the challenges climate change editing for crop and livestock improve- practices did much to help meet the poses to agriculture, genome editing ment has the potential to substantially increasing food, fiber, feed, and fuel for crop and livestock improvement is contribute to human welfare and sustain- needs of a burgeoning world population. garnering increasing attention. This issue ability and that successful deployment As population growth continues through paper describes how genome editing of genome editing in agriculture will this century, those needs continue to is performed, the types of “edits” that benefit from science-informed, value- increase while the amount of land and can be made, how the process relates to attentive regulation that promotes both water available for production decreases. traditional breeding and conventional innovation and transparency (alongside In addition, climate change is impacting genetic engineering, and the potential strategies to improve food distribution, land and water availability further and This material is based upon work supported by the U.S. Department of Agriculture’s (USDA) Agricultural Research Service (ARS) and Animal and Plant Health Inspection Service (APHIS) Agreement No. 59-0202-5-002. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of USDA–ARS, USDA–APHIS, any other USDA agency, or the USDA. CAST Issue Paper 60 Task Force Members Task Force Jennifer Kuzma, School of Public and Task Force Reviewers International Affairs, North Carolina Adam J. Bogdanove, Chair, Section State University, Raleigh Val Giddings, Information Tech- of Plant Pathology and Plant-Microbe nology and Innovation Foundation, Biology, School of Integrative Plant Katia Pauwels, Biosafety and Biotech- Washington, D.C. Science, Cornell University, Ithaca, nology, Sciensano, Brussels, Belgium New York Greg Gocal, Research and Develop- Steven H. Strauss, Department of Forest ment, Cibus, San Diego, California David M. Donovan, Animal Biosci- Ecosystems and Society, Oregon State ences and Biotechnology Laboratory, University, Corvallis Joseph F. Petolino, Dow AgroSci- USDA–ARS/NEA, Beltsville, Mary- ences, Indianapolis, Indiana (retired) land (retired) Daniel F. Voytas, Department of Genet- ics, Cell Biology, and Development/Cen- CAST Liaison Estefania Elorriaga, Department of ter for Genome Engineering, University Forest Ecosystems and Society, Or- of Minnesota, Minneapolis David Songstad, Cell Biology, Cibus, egon State University, Corvallis San Diego, California altering the incidence of droughts, floods, cells and organisms. Advances in recent foundation for informed regulatory and and other severe weather events, as well years have made genome editing appli- policy decision-making and for consumer as the distribution and prevalence of cable in many contexts and for many choice. diseases and pests. Meeting the increas- purposes, including plant and animal ing needs of the world population in the improvement. This issue paper describes GENOME EDITING face of these challenges, sustainably, is a how genome editing is performed, the daunting yet essential task. types of “edits” that can be made, how METHODS Continued successes in crop and live- the process compares to traditional breed- Genome editing, as it is most frequent- stock improvement will be critical. Re- ing and conventional genetic engineering, ly practiced, uses reagents that specifi- sistance to pests and diseases, tolerance and the potential limitations of the ap- cally recognize and precisely cleave DNA to adverse environmental conditions, proach. This paper also touches on ways targets within the genomes of living and improved nutritional quality will be in which genome editing can enhance cells (Voytas 2013). These reagents are essential. In addition, adapting plants to related technologies such as the insertion referred to as site-directed nucleases increase their efficacy for environmental of transgenes for genetic modification (SDNs; also called sequence-specific remediation and improving animals for of plants and animals. Following these nucleases or SSNs). SDN-induced DNA use as models for human disease will sections, the paper presents an overview damage is perceived by the cell and be important. Meeting the needs of the of the current landscape of governance of repaired; however, it is possible to direct increasing world population will also genome editing in selected countries, in- the cell’s DNA repair mechanisms to depend on social and engineering innova- cluding existing regulations, international incorporate desired gene edits at or near tions, including changes to improve food agreements, and standards and codes of the break site. In this section, the types distribution, decrease socioeconomic conduct. Gene drives, a new and widely of SDNs that have been developed to disparities, mitigate barriers to trade, and discussed implementation of genome achieve targeted DNA cleavage, as well moderate political and market dependen- editing (Esvelt et al. 2014; Saey 2015; as the variety of targeted DNA modifica- cies. The power of genome editing,1 how- Wade 2015) that can modify the genetics tions that can be realized through their ever, suggests that, if conducive social of a wild population for purposes such as use, are described briefly. and regulatory conditions are in place, pest control, raise a unique and complex it can substantially increase the positive set of biosafety and regulatory issues Gene-targeting Reagents impacts of plant and animal breeding on beyond the scope of this paper and are Three types of SDNs—meganucle- human welfare and sustainability. not discussed. ases, zinc-finger nucleases (ZFNs), and Genome editing is the process of The paper is intended to be a resource transcription activator-like effector making precisely targeted changes in the for U.S. and international regulatory nucleases (TALENs)—recognize their DNA (deoxyribonucleic acid) of living agencies, policy- and lawmakers, private DNA targets through protein/DNA inter- and public research institutions, industry, actions. The DNA recognition domains of 1 Italicized terms (except genus/species names and and the general public. It aims to pro- these reagents are engineered to achieve published material titles) are defined in the Glossary. vide a conceptual and knowledge-based requisite target specificity. 2 COUNCIL FOR AGRICULTURAL SCIENCE AND TECHNOLOGY Meganucleases, produced by many elucidated (Boch et al. 2009; Moscou the mismatch is repaired based on the prokaryotes and algae, typically recog- and Bogdanove 2009), the TAL effec- oligonucleotide sequence, specific base nize and cleave DNA sequence signa- tor DNA recognition domain is used to modifications are made in the genome. tures ranging from 12 to 40 base pairs create targeted nucleases for gene editing Oligonucleotide-directed mutagenesis (bp) in length (Paques and Duchateau (Christian et al. 2010). The TAL effector (ODM) is therefore an alternative to 2007; Smith et al. 2006). Whereas each DNA recognition domain is structurally nuclease-based gene editing. meganuclease has evolved its own DNA modular, with a pair of variable amino sequence specificity, they can be engi- acids in each module specifying a single neered to recognize new DNA target nucleotide in the target DNA sequence. Types of DNA Modifications sites. Engineering meganucleases for ge- Thus TALENs can be readily engineered Created with SDNs nome editing is often challenging because for desired specificity by assembling the Although there are a variety of SDN the amino acids that
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