1. REGULATION OF PRECISION BREEDING TECHNOLOGIES: CHALLENGES AND OPPORTUNITIES
Harvey Glick
Monsanto Company

2. PRESENTATION OVERVIEW
OVERVIEW OF PRECISION BREEDING INNOVATIONS (PBI)
DISCUSSION OF GENE EDITING
HIGHLIGHTS OF GLOBAL REGULATORY DISCUSSION
REGULATORY CONSIDERATIONS

3. EVOLUTION OF PLANT BREEDING

4. Create Genetic Variability*
Create Genetic Variability
Create Genetic Variability
07/16/96
Phil Simon, ARS
Photos: Corbis *

5. PRECISION BREEDING INNOVATIONS
Site-Directed Nucleases (SDNs)
Zinc-finger nucleases
TALEN
CRISPR/Cas9
CRISPR/Cpf1
Oligonucleotide directed mutagenesis (ODM)
Cisgenics
Intragenics
Agroinfiltration
RNA-Directed DNA Methylation
Reverse Breeding
Grafting (non GE on GE rootstock)
By Keith Weller, USDA [Public domain], via Wikimedia Commons
May use genome editing
By User Larsinio on en.wikipedia [Public domain], via Wikimedia Commons

6. How does it work? CRISPR-CAS Example
Cas9 nuclease (DNA cutting enzyme)
Guide RNA is designed to direct Cas9 enzyme to the DNA sequence of interest
Cas9 enzyme binds to the targeted DNA and makes double strand break
Target Sequence
DNA double strand break is repaired through a plant’s own cellular process
Guide RNA
Guide RNA matches the target DNA sequence
CRISPR-Cas Applications 4

7. Harnessing DNA break repair mechanisms for genome editing
Site-directed nuclease creates DNA
double strand break
SDN
Non-homologous end
joining
Site-directed mutagenesis
Homologous recombination
Endogenous genes
GOI
Templated editing
Site-directed insertion
Endogenous genes
Cis/Transgenes

8. GENE EDITING OPPORTUNITIES
More Sustainable Production
More efficient use of water and nutrients
Ability to grow on ‘poorer quality’ soils
Increased temperature tolerance
Improved photosynthetic capacity
Reduced use of inputs

9. GENE EDITING OPPORTUNITIES
Tomato
-Disease
Resistance
Reducing Allergens
Research is being done on deleting gluten genes in wheat so people with gluten sensitivities can eat bread and baked goods made with wheat flour.

10. GENE EDITING OPPORTUNITIES
Producing Fruits & Vegetables with Better Taste, Appearance and Nutrition
Brighter colors and sweeter flavors
Higher levels of beneficial nutrients, like antioxidants, carotenoids and lycopene
Disease
Tomato
-Disease
Resistance
Increasing Resistance to Disease
Using naturally occurring characteristics within a plant’s own family, plant scientists can produce vegetables with disease resistance. Eg: Downy mildew in spinach, fungal disease in tomato and citrus greening in oranges

11. REGULATORY CONSIDERATIONS

12. GENOME EDITING: A CONTINUUM
Conventional breeding: combines many genes/mutations at once X
Small changes up to major chromosomal re-arrangements and
deletions. Extensive backcrossing to reduce linkage drag
Genome editing: Targeted mutagenesis & site-directed gene insertion
TTC CAG AGT AAC TTC
Specific changes at pre-selected genomic locations. Small changes up to
major chromosomal re-arrangements and deletions. Targeted
transgenesis and cisgenesis
Transgenesis: Random introduction of specific genes
Insertion of transgenes into the genome for a predictable
outcome/trait

13. Degree of Regulation GENOME EDITING APPLICATIONS
GLOBAL OPINIONS* ON THE REGULATORY STATUS SUGGEST A CONTINUUM WITH POORLY DEFINED BOUNDARIES
Random
Transgene
Integration
Traditional
Breeding/
mutagenesis
Degree of Regulation
Site-directed
Mutagenesis
Templated
Gene Editing
Site-directed
Transgene Insertion
GENOME EDITING APPLICATIONS *
EFSA 2012
FSANZ NPBT Workshop 2013
International Seed Federation (ISF)
European Academies’ Scientific Advisory Council 2017

14. Regulators are striving for consistent policy outcomes across diverse regulatory systems and existing GM definitions
Argentina
Regulatory policy sets case-by-case exemption
Trigger for regulation as GMO: “new combination of genetic material”
Consultation process: 60 days
So far: not regulated as GMO
Japan
Case-by-case approach, evolving policy
So far: not regulated as GMO
Australia
Technical expert opinion: no new concerns
Trigger for regulation as GMO: “introduced foreign DNA”
Regulatory draft guidance under review
So far: waiting for final regulation

15. Regulators are striving for consistent policy outcomes across diverse regulatory systems and existing GM definitions
European Union
Process-based GMO regulation: 2001/18/EC
EU Court of Justice’s decision on regulatory status expected in early 2018
So far: pre-2015 technical opinions on ODM Canola
Not regulated as GMO: Sweden, Finland, UK, Spain, Germany, Belgium, Netherlands
Regulated as GMO: Czech Republic
Canada
Product-based regulation: case-by-case assessment irrespective of process
Trigger: novelty of trait
So far: regulated as novel trait (ODM canola

16. Rest of the world: Initial discussions & policy-
Regulators are striving for consistent policy outcomes across diverse regulatory systems and existing GM definitions
United States
USDA (current regulations, currently under review)
Case-by-case determination
Trigger for regulation as GMO: “insertion of plant pest sequences”
Letter of Inquiry (LOI) process: ~6 months
So far: not regulated as genetically engineered plant
FDA
Voluntary process covers new crop varieties
EPA
Considering if pesticidal products derived from genome editing techniques are within the conventional breeding exemption
Rest of the world: Initial discussions & policy-
setting stages

17. REGULATORY POLICY CONSIDERATIONS
Plant varieties developed using precision breeding methods should not be differentially regulated if they are similar or indistinguishable from varieties that could have been produced through earlier breeding methods

18. REGULATORY POLICY CONSIDERATIONS
Pre-market food, feed and environmental safety assessments should be driven by the characteristics of the product rather than on the process used to produce the product

19. REGULATORY POLICY CONSIDERATIONS
Global consistency in regulatory approaches to avoid a patchwork of legal frameworks that could stifle innovation and disrupt commodity trade

20. International Consistency is Key
Global movement of ag products
Continued innovation & ag development
Introduction of crop innovations in smaller
or niche markets
It is key that governments and international organizations work together to avoid creating new trade barriers or disruptions due to inconsistent policies and practices.

21. REGULATION OF PRECISION BREEDING TECHNOLOGIES: CHALLENGES AND OPPORTUNITIES
Harvey Glick
Monsanto Company