Biosafety Assessment and Regulations of Gene Editing by Dr. Vibha Ahuja during the Regional Expert Consultation on Gene Editing in Agriculture and its Regulations Technical Session III

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Dr. Vibha Ahuja
Biotech Consortium India Limited

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 Gene editing describes a variety of molecular biology applications
that enable targeted and precise alterations of the genomes of
plants, animals and microorganisms, but
 No single definition
 No definitive list :varied techniques included.
 Most definitions incorporate the idea of making targeted changes at a known location
 Many agree that these changes are small but there is no shared
definition of “small”
 Also referred to as ‘New Plant Breeding Techniques’ or ‘Genome
Editing Techniques’

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Traits produced are generally possible to produce through
conventional breeding
Gene editing tools allow the generation of these traits much more
efficiently.Gene editing doesn’t necessarily allow us to do things that
weren’t possible before
◦ It makes them possible to do more easily
◦ With greater precision
Most methods of gene editing require a transgenic intermediate step
◦ A transformed plant expresses the gene editing machinery
◦ But no transgenes are present in the final product
Some methods can be accomplished in cell culture, without any
need to transform plants

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Most of the ongoing debate around regulation of gene edited plants
has focused on whether they will be considered GMOs
How to do a risk assessment for a gene edited plant?

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 If there is no novel RNA or protein. Should it be categorized as
genetically engineered and subject to regulation as a genetically
engineered organism?
 Is the existing risk assessment framework necessary for the safety
assessment of gene edited organisms?
 Would all information typical of conducting risk assessments for
novel organisms be required for gene edited plants?

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◦ The products of gene editing have traits that are possible to create, at
random, through conventional breeding methods
◦ Given enough time
◦ But have far fewer unintended effects in the genome than conventional breeding methods
◦ Unintended genomic effects are much less extensive than conventional
breeding methods which have a history of safe use
◦ Similarly, the generated phenotypes could be produced through conventional
breeding methods (for the most part) and would not be subject to risk
assessment

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Molecular characterizations
◦ Insertion site is known. Very simple molecular characterization should be possible
◦ “Off target” cutting is frequently mentioned
◦ But this is guaranteed to be far less extensive than chemical or radiation mutagenesis
Characteristics of the introduced trait
◦ There is no transgene
◦ No “novel” protein is expressed
Agrophenotypic characterization
◦ Should only be required to assess the introduced/edited trait
◦ Collecting huge amounts of measurements to assess potential unintended effects
is not necessary
CAN BE USED, BUT IS IT WORTHWHILE

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Can genetic detection techniques be employed to differentiate
between gene edited product and a similar product obtained by
conventional breeding?
An unknown, undisclosed modification which does not involve the
incorporation of foreign sequences will be hard to detect and even if
is detected, identifying how it was introduced,i.e targeted mutation
using genome editing tools, conventional breeding,including random
mutagenesis,or naturally occurring mutations is impossible.

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There is no way to prove that a genomic change is the result of gene editing
by examining the phenotype
Detection requires knowledge of the specific gene edits that has been made
Molecularly small nucleotide replacements,insertions or deletions are
identical, whether they occurred spontaneously ,were induced by classicle
mutagenesis or site specifically introduced via genome editing
Enforcement of any regulations will be exceedingly difficult in most cases of
gene editing, unless a foreign DNA originating from a noncrossable,sextually
incompatible organism
Effectively looking at voluntary compliance
What will be the effect of unenforceable regulations on public trust ,the rule
of law, scientific innovation and fairness to the regulated community ?
Only those products such as SDN 3 with foreign DNA , where detection is
possible may be subjected to safety assessment

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Free global trade requires internationally harmonized regulations
Different GMO definitions and therefore different regulation and
authorization requirements would hinder international exchange
especially if products are indistinguishable
Need to streamline and increase collaboration amongst regulatory
authorities
Urgent need for international/regional harmonization

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Gene-editing has come up in the discussions under the Cartagena
Protocol as a potential ‘issue’ requiring further risk assessment
guidance.
Everywhere that it was mentioned in the recommendations to
COP14MOP9, it was [bracketed].
Parties did not agree that it should be a specific issue.

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Gene-editing is too broad to consider as ‘one’ issue.
Applications of gene-editing must be considered on a case-by-case
basis.
Many applications of gene-editing would likely NOT meet the criteria
for the need to develop separate/additional guidance on risk
assessment.
Living modified organisms produced through gene-editing do NOT
pose challenges to existing risk assessment frameworks, guidance
and methodologies.
Hence gene editing not included in the decision for separate
guidance

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In India all GMOs and products thereof are regulated under
Rules for the Manufacture, Use, Import, Export and Storage
of Hazardous Microorganisms/ Genetically Engineered
Organisms or Cells, 1989 (Rules, 1989)”
These rules have been notified under the Environment
(Protection) Act, 1986.

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The 1989 Rules cover
Manufacture, import and storage of microorganisms
and gene technological products
Genetically engineered organisms/microorganisms
and cells and correspondingly to any substance and
products and food stuffs, etc., of which such cells,
organisms or tissues form part
New gene technologies in addition to cell
hybridization and genetic engineering

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“Gene Technology” means the application of the gene technique
called genetic engineering, include self cloning and deletion as
well as cell hybridisation;
“Genetic engineering” means the technique by which heritable
material, which does not usually occur or will not occur naturally
in the organism or cell concerned, generated outside the organism
or the cell is inserted into said cell or organism. It shall also mean
the formation of new combinations of genetic material by
incorporation of a cell into a host cell, where they occur naturally
(self cloning) as well as modification of an organism or in a cell by
deletion and removal of parts of the heritable material;

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Regulations and Guidelines on Biosafety of Recombinant DNA Research and
Biocontainment, 2017 (issued by DBT) have reference to gene editing under Plant
Containment
◦ Experiments involving genome editing leading to SDN1-type mutations that are
genetically indistinguishable from organisms which could have occurred naturally
have been covered under Plant Biosafety Level 1 (PBSL-1).
◦ Experiments involving genome editing leading to SDN2 and 3 -type modifications
covered under PBSL-2.
Permission from IBSC is required before initiating the experiments in case of PBSL-
2, whereas intimation to the IBSC member secretary is required in case of PBSL-1. In
certain cases, additional containment may be required and should be discussed with
IBSC before initiation of work.

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South Asia Biosafety Programme
Dr Andrew Roberts, ILSI Research Foundation

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