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16 March 2016, Paris INSERM WORKSHOP - FOSTERING RESPONSIBLE RESEARCH WITH CRISPR-Cas9 1 Human genome editing: Scientific and ethical considerations Bärbel Friedrich German National Academy of Sciences Leopoldina

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Page 1: Human genome editing: Scientific and ethical considerations · The CRISPR-Cas9 system CRISPR: ... • first published genome editing experiments on human embryos • changing the

16 March 2016, Paris INSERM WORKSHOP - FOSTERING RESPONSIBLE RESEARCH WITH CRISPR-Cas9 1

Human genome editing: Scientific and ethical considerations

Bärbel Friedrich German National Academy of Sciences

Leopoldina

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• Founded in 1652, one of the oldest Academy of Sciences worldwide

• 2008 appointed as National Academy of Sciences

• Mission is dedicated to the advancement of science for the benefit of humankind and a better future

• Represents the German scientific community in international committees

• Contributes independent, science-based advice to the government, policy-makers and civil society on key issues, covering all scientific disciplines

German National Academy of Sciences Leopoldina

Residence of the Leopoldina in Halle (Saale)

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The opportunities and limits of genome editing (statement, September 2015)

Genome editing technologies

Possible applications

Legal and ethic considerations

Conclusions and recommendations

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Scientific background of genome editing technologies

Perspectives of applications

Legal and ethical considerations

International summit on human gene editing,

December 2015

Outline

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Genome editing

Genome editing offers the promise to perform a sort of genetic surgery, going into the

human genome of 3 billion positions, so-called nucleotides.

By using these techniques site-directed exchanges, deletions or insertions of

nucleotides may be generateted.

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Features of genome editing tools

A) The 3 nucleases recognize specific DNA sequences B) Cleavage of the DNA C) Endogenous repair systems are activated, leading to: strand religation, insertions, deletions or exchange of designed donor fragments

van der Oost. Science (2013) 339:768.

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Science 337: 816-821 (2012).

The CRISPR-Cas9 system

CRISPR: Clustered Regulatory Interspaced Short Palindromic Repeats CRISPR-associated protein-9 nuclease (Cas9)

Jennifer Doudna Emanuelle Charpentier

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Source: www.neb.com

CRISPR-Cas9 as a tool

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Microorganisms – bioeconomy

Plant breeding

Animal breeding

Modifications of populations in the environment (gene drive)

Animals as organ donors for xenotransplantation

Somatic genetic changes for therapy

Germline interventions

Perspectives of applications

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Modification of mosquito populations by gene drive to fight against infectious diseases

Hammond et al. Nature biotech. 34.1 (2016): 78-83.

Gantz et al. PNAS 112.49 (2015)

Reducing the reproductive capability of the insect vector

Blocking parasite development in the insect

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Animal as organ donors for xenotransplantation

Yang et al. Science 350.6264 (2015): 1101-1104

62 copies of PERVs in the porcine genome

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Human health

There is a need to distinguish between the use of genome

editing in basic research and in clinical application.

There is a need to distinguish between the use of genome

editing in somatic cells and in germ lines.

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Source: www.sangamo.com/pipeline/index.html

Studies for somatic gene therapy

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HIV attacks a type of immune cell known as a T cell (shown here) via a protein encoded by the CCR5 gene.

A clinical trial has shown that a gene-editing technique can be safe and effective in humans. Tebas, P. et al. The New England Journal of Medicine 370, 901-910, 2014

Gene editing techniques alter immune cells

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Somatic Gene Therapy of Duchenne muscular dystrophy

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Long et al. Science 351, 400-403, 2016 (E.N. Olson´s lab)

Somatic Gene Therapy of Duchenne muscular dystrophy

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Development 142.18 (2015): 3151-3165.

Differences in human and mouse embryo gene expression

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Liang et al. Protein & cell 6 (April 2015): 363-372

• first published genome editing experiments on human embryos

• changing the β-globin gene in tripronuclear zygotes responsible for beta thalassemia

low efficiency and off-target effects

Research on human embryonic cells

2016/02 UK scientists gain licence to edit genes in healthy human embryos (Kathy Niakan, FrancisCrick Insitute )

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Legal and ethic considerations

German Embryo protection act - Section 5 Artificial alteration of human germ line cells (1) Anyone who artificially alters the genetic information of a human germ line cell will be punished with imprisonment up to five years or a fine. (2) Likewise anyone will be punished who uses a human germ cell with artificially altered genetic information for fertilisation. (3) … (4) Paragraph 1 does not apply to: an artificial alteration of the genetic information of a germ cell situated outside the body, if any use of it for fertilisation has been ruled out ... Does (4) imply that research can be conducted with altered germ line cells, provided they are not used for implantation? No! The stem cell act clearly prohibits the generation of embryos for research in Germany

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Reports of the German Science Academies and DFG

1. The academies consider genome editing as an important and valuable tool for the alteration of genetic information in practically all living beings. The new techniques promise more efficient, more targeted and thus more controllable genetic modifications with up to now unprecedented accuracy and precision. New dimensions are opened by genome editing for fundamental molecular biological research and potential applications in industrial biotechnology using microorganisms and in agriculture using animal and plants. The academies strongly support basic research on genome editing, which should not be halted or hampered. Such studies are expected to have tremendous benefits also for biomedical applications.

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Statement by the German Science Academies and DFG

2. According to the Leopoldina and its partners a distinction is necessary so far as genome editing in humans is concerned. Research on human somatic cells does not, in principle, pose any ethical or legal problems. The academies see a high potential and benefit in somatic gene therapy. Promising applications for somatic gene therapy already appear on the horizon. However, before the new genome editing techniques can be routinely used in the clinic, more basic medical research is required to lower potential risks of off-target effects and to increase specificity and efficiency of these technologies.

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Statement by the German Science Academies and DFG

3. Applications of germ line therapy, for which the technology is definitely not mature at the present time, is up for discussion. Apart from the legal situation in Germany, which prohibits germ line interventions, the Leopoldina and its partners support the call for an international moratorium for germ line experiments in humans. The period of the moratorium should be used for further research (which can only partially be conducted in Germany due to legal restrictions ) to elucidate the opportunities, the demands and risks of the technology, providing time for a social debate on the ethical, legal and regulatory impacts of germ line therapy. Provided the experimental thresholds are met, the questions arise, how to distinguish between medically based treatment and enhancement of human capabilities and what kind of genome editing in human reproductive applications should be approved. To address these issues the establishment of a model regulatory framework, that could be adopted internationally, seems to be a highly desirable goal.

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Citation of Conclusions Organized by:

Chinese Academy of Sciences. The Royal Society U.S. National Academy of Sciences U.S. National Academy of Medicine

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So far as somatic gene therapy is concerned:

Citation of Conclusions

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With respect to germline interventions:

Citation of Conclusions

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Citation of Conclusions

No support for a moratorium, but ........

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The final conclusion: There is a need for a societal discourse and the establishment of an international forum

Citation of Conclusions

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“It´s no longer possible to control technologies by the laws of one country. If there is a demand for a technology, people will go whichever country has it”

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Merci pour votre attention