Presented by:

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: steffi.FRIEDRICHS@oecd.org Skype: steffifriedrichs