THE AGE OF GENE EDITING - oecd.org 1_ Friedrichs _BNCT... · Taken from: . Benefits arising from...
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THE AGE OF GENE EDITING
25th February 2016
Steffi Friedrichs
OECD Working Party on Biotechnology, Nanotechnology and Converging Technologies (BNCT)
Outline – Gene Editing 101
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• What is it? - Technological Advances
• Who is doing it? – the main Players
• What is it used for? – current (and future) Applications and
Products
• Why are we talking about it? – the Policy Issues surrounding
Gene Editing:
– IP issues (i.e. Patents, Open Science, etc.)
– Risks and Benefits
– Regulatory Issues (e.g. applicability of GM Regulation)
– Public Acceptance
What is Gene Editing?
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• Gene/Genome Editing:
– High-precision manipulation of individual strands of DNA (i.e.
at the ‘byte’-level of information storage in organic life)
– Currently, three main techniques are used:
Taken from: http://www.technologyreview.com/review/524451/genome-surgery/
“Collectively these technologies have created a scientific paradigm that envisions the genome as an infinitely
editable piece of software.” (Gersbach, 2014).
What is Gene Editing?
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• Gene/Genome Editing:
– High-precision manipulation of individual strands of DNA (i.e.
at the ‘byte’-level of information storage in organic life)
– Currently, three main techniques are used:
Taken from: http://www.technologyreview.com/review/524451/genome-surgery/
“Collectively these technologies have created a scientific paradigm that envisions the genome as an infinitely
editable piece of software.” (Gersbach, 2014).
See: Report of the Workshop on Environmental Risk Assessment
of products derived from New Plant Breeding Techniques
(February 2014), OECD Series on Harmonisation of Regulatory
Oversight in Biotechnology, No. 61, ENV/JM/ MONO(2016)5.
CRISPR:
Clustered Regularly-Interspaced
Short Palindromic Repeats
How does Gene Editing work?
Example: CRISPR-Cas9
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1. Sequencing of a genome
(i.e. the DNA-code is read) … 2. The gene editing toolset is created (by adapting an
existing defence mechanism used by bacteria):
Target-DNA (i.e. DNA
to be edited)
Nuclease (i.e. enzyme
that cuts DNA)
Guide-RNA
(attached to nuclease)
3. The Guide-RNA unzips the Target-DNA,
and the Nuclease cuts the Target-DNA.
Option 2: insertion of a new DNA strand
Option 1: switching off the entire gene (‘KO’)
Taken from: https://www.youtube.com/watch?v=2pp17E4E-O8
Youtube clip by Mc Govern Institute for Brain Research at MIT.
non-GMO!?
non-detectable
The main Players in Gene Editing
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… and their work:
Source: The Economist ‘Genome editing - The age of the red pen’, 22.08.2015.
Applications of Gene Editing (1)
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Current Applications:
• Health / Medicine:
– Fast, targeted breeding of mouse models (e.g. 2 years shortened to 4 months) for advanced understanding of the roles of specific genomes and cures for genetic disorders, or for fertility studies with human embryo cells (cf. Francis Crick Institute, UK, February 2016)
– Study of the gene-editing tool itself (i.e. safety issues, off-target effects, efficacy, etc.) (cf. China, April 2015)
– Trials to eradicate malaria-transmitting mosquitos (by making them infertile / preventing mating / infecting them with bacteria / etc.)
• Agriculture:
– Fast, targeted breeding of plants with special resistances (e.g. drought resistance), or with special abilities (e.g. self-fertilization or self-pollination), or for special purposes (e.g. therapeutic applications)
• Environment:
– Studies to inhibit the spreading of invasive species (e.g. farmed salmon)
Applications of Gene Editing (2)
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(potential) Future Applications:
• Health / Medicine:
– Treatment of diseases (i.e. by elimination of genetic mutations that cause a disease, or by modification of human somatic (i.e. non-reproductive) cells): HIV/Aids, haemophilia, sickle-cell-anaemia, some cancers, etc.
– Elimination of heritable genetic diseases from a family line (i.e. by KO- or repair of the human germ line in embryonic cells)
• Agriculture:
– Fast, targeted and ‘cheap’ breeding of plants and animals with specific desirable attributes (cf. super-muscly pigs created by deleting a gene, which inhibits muscle growth, versus the Belgian Blue beef bred through traditional breeding techniques)
Taken from: http://www.nature.com/news/super-muscly-pigs-created-by-small-genetic-tweak-1.17874
“Super-muscly pigs created by small genetic tweak.” (Nature 523 (2015) 13-14).
IP Issues arising from Gene Editing:
Patentability and Priority
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Patent applications relating to CRISPR-Cas9:
– Northwestern University in September 2008 (Erik Sontheimer and
Luciano Marraffini, 61/099,317);
– Vilnius University in March 2012 (Virginijus Siksnys and others,
61/613,373);
– UC Berkeley in May 2012 (Jennifer Doudna and others,
61/652,086); and
– ToolGen in October 2012 (Jin Soo Kim and others, 61/717,324)
– Broad Institute, MIT, in December 2012 (Feng Zhang and others,
8,697,359)
Rejected by
USPTO
USPTO pending
Rejected by
USPTO
Rejected by
USPTO
Granted by USPTO
(April 2014)
• 11th January 2016: declaration of interference between Doudna’s patent
application and Zhang’s issued patents
• 16th February 2016: Caribou Biosciences Inc., co-founded by Doudna, wins a
patent on ‘Compositions and methods of nucleic acid-targeting nucleic acids’
(i.e. it does not mention Cas9)
IP Issues arising from Gene Editing:
Patent Values and Economics
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In August 2015, several high-profile investors,
including the Bill & Melinda Gates Foundation
and Google Ventures, pumped US$120
million into the genome-editing firm Editas
Medicine of Cambridge, Massachusetts. Big
Agriculture is following suit: DuPont forged an
alliance with the genome-editing firm Caribou
Biosciences in October, and announced its
intention to use CRISPR–Cas9 technology to
engineer crops.
• 11th January 2016: declaration of interference between Doudna’s patent
application and Zhang’s issued patents
• 16th February 2016: Caribou Biosciences Inc., co-founded by Doudna, wins a
patent on ‘Compositions and methods of nucleic acid-targeting nucleic acids’
(i.e. it does not mention Cas9)
• Worries about ‘Evergreening’ of gene-editing patents
In 2011, Caribou Biosciences
Inc. raised USD$11 million for
cell-engineering, drug screening
and agricultural and industrial
biotech.
Potential Safety Issues
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• Off-target edits/mutations
• Unknown effects, such as:
– In agriculture: creation of poisons
– In mammals: diseases/defects (e.g. gene tp53 expresses a tumor-suppressing
protein (p53), which also causes premature ageing)
Taken from: http://www.origene.com/CRISPR-CAS9/Product.aspx?SKU=KN200003
Benefits arising from Gene Editing
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• Fast eradication of malaria-carrying mosquitos (~ 3.2 billion people – nearly
half of the world's population – are at risk of malaria. ~ 438 000 malaria
deaths (in 2015) … these numbers already represent a 60% decrease in
mortality rates due to increased prevention).
• Gene-editing studies provide insights into fertility:
– 2/3 of human embryos fail to develop successfully,
– every year, 7.9m children, 6% of total births worldwide, are born with a serious defects of
genetic origin
• Reduction of time (and cost) of traditional breeding techniques, while
providing the same results (i.e. products are indistinguishable from those
resulting from traditional breeding techniques).
• Pharma companies hope to explore the function of every gene in the
human genome.
[1] Source: Financial Times (January 2016): http://www.ft.com/cms/s/0/9fd0529e-bb6a-11e5-b151-8e15c9a029fb.html#ixzz40tvGgvHr
Regulatory Issues arising
from Gene Editing
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• Since April 2015: EU is contemplating, if gene-edited plants should be
classified as ‘genetically modified’ (i.e. GMOs)
The final verdict is expected towards the end of March 2016
Some gene-editing products have already been confirmed as non-GMO by
several countries (i.e. US, Canada, Germany, Sweden, Argentina, …)
The PROBLEM: the gene-editing technique can be used in different ways,
resulting in some products that are GMO and others that are not
The EU Food Safety Authority (EFSA) noted that all ‘non-natural’ plants
would be classed as GM, but:
“You can tell if a crop has been genetically modified, but it is impossible to tell
if a plant has been subject to gene editing. It is closer to old-fashioned
breeding techniques than it is to genetic modification technology.”
(Professor Wendy Harwood, John-Innes Centre, UK)
Ethical Issues arising from Gene Editing
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• ‘Playing God’: gene-editing is fast and easy (i.e. readily available and
applicable toolkit)
• The boundaries to ‘creating life’ are blurred: why stop at the insertion of
naturally occurring genetic variants? Why not create/write new
variants/DNA-code with synthetic biology? (e.g. programme cells to die, if
they become cancerous)
• The boundaries of curable diseases/defects and fixable disabilities are
blurred; a new form of ‘eugenics’ might devalue the humanity of the
disabled
• The danger of over-hype: similar to stem-cell therapies, expectations might
be too high and must be managed
THANK YOU! Steffi Friedrichs Biotechnology, Nanotechnology and Converging Technologies t: + (33-1) 85 55 60 27 e: [email protected] Skype: steffifriedrichs