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Genome Editing in Agriculture

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Genome Editing in Agriculture Council for Agricultural Science and Technology Kent G. Schescke Executive Vice President 2018 The CAST Mission The CAST Vision A world where decision making related to agriculture and natural resources is based on credible information developed through reason, science, and consensus building. What Does CAST Do? • CAST disseminates science- based information through: o Print materials o Online sources o Videos on website, YouTube, and SchoolTube o Spanish and Chinese translations of select publications How Does CAST Do This? With the help of many volunteer contributors: • 50 Board Members representing scientific societies, companies, nonprofits, and 65% academia universities 15% government • 160+ active task force members working on 15% companies CAST reports yet to be released 5% nonprofits • Volunteer scientific experts as authors and reviewers—more than 700 volunteers since 2007 Unique Formats for Unique Needs • Issue Papers. 8-20 pages; more narrowly focused. • Special Publications. 25-150 pages; often follow-on to workshop. • Task Force Reports. 40-200 pages; comprehensive overview. • Commentaries. 4-8 pages; quick turnaround. • Ag QuickCASTs. 1-page excerpts from full CAST publications. Other Forthcoming Publications • Impact of Free-Range Poultry Production Systems on Animal Health, Human Health, Productivity, Environment, Food Safety, and Animal Welfare Issues [July 2018 rollout] • Food Loss and Waste [Summer 2018 rollout] Friday Notes •Published 48 times annually •Lead articles on timely ag topics •Dozens of ag news briefs from 100+ sources with live links to original articles •An international news section •Legislative updates from D.C. CAST Welcomes Your Suggestions CAST welcomes suggestions, ideas, and recommendations for future CAST publications and projects. Anyone—whether a CAST member or nonmember—may submit a proposal for consideration, using the CAST Proposal Form. Visit CAST Online at www.cast-science.org Sun…Earth…Water…Mankind. In synergy with science and The CAST website has technology to create a had visitors from every sustainable world supported U.S. state, Canada by plants and animals. provinces, and 181 countries. Presented by Adam J. Bogdanove, Ph.D. Section of Plant Pathology and Plant-Microbe Biology School of Integrative Plant Science Cornell University JUNE 2018 Task Force Members Authors: Reviewers: Adam J. Bogdanove (Chair) Val Giddings ◦ Cornell University, Ithaca, NY ◦ Information Technology and Innovation David Donovan Foundation, Washington, D.C. ◦ USDA—ARS/NEA, Beltsville, MD (ret) Greg Gocal Estefania Elorriaga ◦ Cibus, San Diego, CA ◦ Oregon State University, Corvallis Joseph Petolino Jennifer Kuzma ◦ Dow Agrosciences, Indianapolis, IN (ret) ◦ North Carolina State University, Raleigh CAST Liaison: Katia Pauwels David Songstad ◦ Sciensano, Brussels, Belgium ◦ Cibus, San Diego, CA Steven H. Strauss ◦ Oregon State University, Corvallis Daniel F. Voytas ◦ University of Minnesota, Minneapolis Contents Genome editing - methods, tools, types Applications in crops Applications in livestock Genome editing compared to other methods Regulatory landscape Perspectives & Conclusions Q&A/Discussion What is a genome? https://www.youtube.com/watch?v=J9uPeJyR_Ko What is genome editing? technologynetworks.com Genome editing: making targeted sequence changes to a genome Revolutionizing biology Driving discovery and application in medicine, industry, and agriculture Genome editing vids https://www.youtube.com/watch?v=XPDb8tqgfjY https://www.youtube.com/watch?v=2pp17E4E-O8 https://www.youtube.com/watch?v=AJm8PeWkiEU Most common approach Make targeted DNA breaks and harness repair pathways for desired outcome single strand break double strand break DNA breaks • Occur naturally during production of germ line cells; important for recombination during meiosis • Can occur in all cells due to radiation, chemicals • Usually repaired faithfully, but repair can introduce changes… Repair of DNA breaks Non homologous end joining (NHEJ) - Knock out Homology directed repair (HR) - swap - insert Carroll (2014) Annu. Rev. Biochem. Tools: site-directed nucleases (SDNs) to target breaks Homing Endonucleases (“Meganucleases”) FokI Zinc Finger Nucleases FokI FokI TAL Effector Nucleases FokI CRISPR/Cas systems Bogdanove et al. (2018) Nucleic Acids Res. Types: The SDN framework SDN-1 SDN-2 SDN-3 Base editing without double strand breaks Half- APOBEC1 C –> T Adapted from C. Bikel, Science Oct 2017 doi:10.1126/science.aar3226 Oligonucleotide directed mutagenesis (ODM) Sauer et al. (2016) Plant Biotechnol. J. The SDN class framework • Base editing • ODM Applications in Crops Delivery • Introduce SDN-encoding DNA as a transgene, using Agrobacterium or gene gun, then in the next generation find the “null segregant” with the edit but not the transgene • Introduce DNA, mRNA, or protein into single cells (no transgene integration into the genome), then regenerate whole plants. • Deliver SDN-encoding DNA using viruses; favorable if virus can reach meristem cells that give rise to seeds • Transformation, tissue culture and regeneration, and viral vector development are essential. Applications in Crops Biofortification, quality Resistance to disease Processing/storage traits Herbicide tolerance Biomass Male/female sterility Flowering time Applications in Livestock Delivery Into embryos or cultured cells: • Introduce SDN-encoding DNA directly or using a virus • Inject mRNA or protein Cell culture and cloning techniques are essential. Applications in Livestock Productivity • Improved muscling for meat Quality • Reduced allergenicity of milk Animal health and welfare • Genetic removal of horns • Resistance to African Swine Fever Bioreactor • E.g., using eggs for production of proteins Genome Editing Compared to Other Methods Regulatory Landscape US USDA—The process and the product matter • Was plant pest DNA used? Is the product a plant pest or weed? FDA—The trait is the focus • Is the product a drug or a food? Is it safe? EPA—The trait is the focus • Does the trait allow the production of a pesticide? Canada All novel plant traits are regulated equally, regardless of process • Conventional breeding, mutation breeding, transgenesis, and gene editing are treated the same EU The process matters • Was the product made using transgenic technology? Regulatory Landscape Recently in the US • Several USDA-APHIS responses to letter of inquiry re regulatory status of genome edited crops--not subject to review because no plant pest DNA and not weedy. • (Mar-18) U.S. Secretary of Agriculture Sonny Perdue: The USDA “does not regulate or have plans to regulate plants that could otherwise have been developed through traditional breeding techniques as long as they are not plant pests or developed using plant pests.” Regulatory Landscape “New Techniques in Agricultural Biotechnology Working Group” mandated by the European Commission • SDN-1 should be excluded from the European GMO Directive because of its similarity to conventional mutagenesis. • SDN-2 and ODM are equivalent to mutagenesis • No clarity on the size limit to still be SDN-2 • SDN-3 creates new combinations of genetic material and should be covered by GMO directives. Regulatory Landscape European Court of Justice Advocate General M. Bobek opinion in ongoing case: • Some genome-edited organisms need not be regulated in the same way as conventional GM organisms. • SDN-1 and SDN-2 are generally equivalent to mutagenesis, but no clarity on whether integration of a repair template constitutes GM and what size and nature of edits might constitute GM. • A definitive legal interpretation from the European Court of Justice of whether SDN-1 and SDN-2 are to be excluded from the European GMO (GM organism) Directive is expected soon. Perspectives • Economic issues • Provided a conducive intellectual property landscape, genome editing may help small companies and public institutions innovate, particularly in specialty crops or livestock species. • The public • Genome editing is likely to be subject to the same underlying fac- tors of information processing and risk perception that have been found to influence attitudes toward other emerging technologies. • Subject matter experts • Recommendations vary; influenced by perceptions of precision and safety but also by worldviews about technology and society. • Nation States • National priorities, cultural perceptions, politics, and trade issues make harmonization of governance unlikely. Conclusions • The power of genome editing suggests that, if conducive social and regulatory conditions are in place, it can substantially increase the positive impacts of plant and animal breeding on human welfare and sustainability. • Successful deployment of genome editing for crop and livestock improvement will benefit from science-informed, value-attentive regulation that promotes both innovation and transparency. Questions/Discussion Adam Bogdanove [email protected] This CAST Report available @ www.cast-science.org/ publications..
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