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GENE DRIVES a Report on Their Science, Applications, Social Aspects, Ethics and Regulations

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GENE DRIVES a Report on Their Science, Applications, Social Aspects, Ethics and Regulations GENE DRIVES A report on their science, applications, social aspects, ethics and regulations European Network of Scientists for Social and Environmental Responsibility Imprint Publishers: Copyright notice Critical Scientists Switzerland (CSS) This work is licensed under a Creative Commons Dändlikerrain 3 Attribution 4.0 International License (CC BY 4.0 Int 3014 Bern http://creativecommons.org/licenses/by/4.0/). This www.criticalscientists.ch publication may be shared or remixed for commer- [email protected] cial or non-commercial use provided that Critical Scientists Switzerland (CSS), European Network of European Network of Scientists for Social and Scientists for Social and Environmental Responsi- Environmental Responsibility (ENSSER) bility (ENSSER), Vereinigung Deutscher Wissen- Marienstraße 19/20 schaftler (VDW) and/or the corresponding author 10117 Berlin are acknowledged as the source. This notification www.ensser.org does not replace or alter the CC BY 4.0 Int legal text by any means. Vereinigung Deutscher Wissenschaftler (VDW) Marienstraße 19/20 10117 Berlin www.vdw-ev.de Editor: Holly Dressel Layout: Richard Weis, www.piccobello-berlin.de Cover graphic design under CC BY-SA-NC 4.0 Int by Marcel Bamert, www.marcelbamert.ch Printed at: www.wir-machen-druck.de Circulation: 1000 ISBN: 978-3-00-062389-9 Publication date: May 2019 Available for download at: https://genedrives.ch/report This publication is made possible by financial support from Supported by Table of contents Summary ......................................................................................9 Introduction ................................................................................15 Chapter 1: What are Gene Drives? The science, the biology, the techniques .......................21 1 What are Gene Drive Organisms and how do Gene Drives work? ......................... 21 2 Short historical background ............................................................................ 22 3 The breakthrough: the CRISPR/Cas9 or RNA guided Gene Drive system ............... 25 3.0.1 DNA repair mechanisms after double-strand breaks (DSBs) ..........................................26 3.0.2 CRISPR/Cas variants ..................................................................................................26 3.1 Limitations and uncertainties of CRISPR/Cas ........................................................................28 3.2 How does a CRISPR/Cas Gene Drive work? ...........................................................................29 3.3 Limitations, shortcomings and uncertainties of CRISPR/Cas Gene Drives .................................30 3.3.1 Resistance ................................................................................................................30 3.3.2 Inefficiency in plants ...................................................................................................31 3.3.3 Inefficiency in mice ..................................................................................................32 3.3.4 Issues with p53 .........................................................................................................32 3.3.5 CRISPR/Cas off-target effects ....................................................................................32 3.3.6 Invasiveness and potential global reach .......................................................................32 3.3.7 Irreversibility ............................................................................................................33 3.4 CRISPR/Cas as enabler for many Gene Drive systems ...........................................................34 4 Mechanisms and techniques used ................................................................... 34 4.1 Selfish genetic elements: ......................................................................................................35 4.2 Over-replicators / replication-distorters ................................................................................37 4.2.1 Transposable elements (TEs) .....................................................................................38 4.2.2 Homing endonuclease genes (HEGs) ...........................................................................40 4.3 Segregation & transmission distorters ....................................................................................42 4.3.1 Sex-ratio distorters ....................................................................................................44 4.3.2 Underdominance / Heterozygous disadvantage ............................................................46 4.3.3 Toxin-antidote based drives ........................................................................................48 5 Gene Drive categories and attributes, their limitations and risks .......................... 50 5.1 Threshold-dependent, threshold-independent and temporally self-limiting drive systems .........51 5.2 Suppression (elimination/eradication) vs modification ............................................................52 5.3 Removability and reversibility ...............................................................................................52 6 Real problems and the search for safety ............................................................ 54 6.1 Restrictive Gene Drives: (daisy) chain drives, split drives and global vs. local ...........................55 6.2 Gene Drives targeting geographic sequence variants .............................................................57 6.3 Gene Drive ‘catchers’ – ideas and approaches for ‘anti-gene drive’-drives ..............................57 6.4 ‘Immunising’ drives .............................................................................................................57 7 Summary and conclusions ............................................................................... 57 References ....................................................................................................... 60 Table of contents 3 Chapter 2: Potential applications and risks ....................................69 1 General introduction ...................................................................................... 69 2 GDOs - applications under development ........................................................... 72 2.1 Introduction .......................................................................................................................72 2.2 Overview of Gene Drive applications under development .......................................................72 2.2.1 Insects ......................................................................................................................73 2.2.2 Small mammals .........................................................................................................73 2.2.3 Fish, birds, mollusks, nematodes, flatworms & fungi .....................................................74 2.3 Knowledge required to understand the risks of using a species as a GDO .................................88 2.4 Studies and specific applications ..........................................................................................89 2.4.1 Case study 1: Mosquitoes ...........................................................................................89 2.4.2 Case study 2: Mice ..................................................................................................104 2.4.3 Case study 3: Plants in agriculture – Palmer amaranth .................................................112 2.4.4 Agricultural insect pests as Gene Drive targets ...........................................................120 2.4.5 Dual use - military (& civilian) research & potential use ................................................124 3 Risks, potential negative impacts and risk assessment limitations .......................126 3.1 Risk assessment of GDOs .................................................................................................126 3.1.1 Molecular considerations .........................................................................................127 3.1.2 Outcrossing and spreading .......................................................................................128 3.1.3 Risk assessment of the intended effects .....................................................................128 3.1.4 Risk assessment of the unintended effects through escape ..........................................128 3.2 Monitoring ........................................................................................................................129 4 Conclusions ..................................................................................................130 References ......................................................................................................133 Table references ......................................................................................................................138 References Table 2a ..........................................................................................................138 References Table 2b ..........................................................................................................140 References Table 2c ..........................................................................................................141 References for geographic range of target species ......................................................................142 Case study references
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