{"id":1723,"date":"2021-03-30T15:22:14","date_gmt":"2021-03-30T13:22:14","guid":{"rendered":"https:\/\/www.stop-genedrives.eu\/?page_id=1723"},"modified":"2022-07-07T17:41:15","modified_gmt":"2022-07-07T15:41:15","slug":"ecological-risks-2","status":"publish","type":"page","link":"https:\/\/www.stop-genedrives.eu\/en\/ecological-risks-2\/","title":{"rendered":"Ecological risks"},"content":{"rendered":"<p>[vc_row row_height_percent=&#8221;0&#8243; override_padding=&#8221;yes&#8221; h_padding=&#8221;7&#8243; top_padding=&#8221;4&#8243; bottom_padding=&#8221;2&#8243; overlay_alpha=&#8221;50&#8243; gutter_size=&#8221;3&#8243; column_width_percent=&#8221;100&#8243; shift_y=&#8221;0&#8243; z_index=&#8221;0&#8243;][vc_column column_width_percent=&#8221;100&#8243; gutter_size=&#8221;3&#8243; overlay_alpha=&#8221;50&#8243; shift_x=&#8221;0&#8243; shift_y=&#8221;0&#8243; shift_y_down=&#8221;0&#8243; z_index=&#8221;0&#8243; medium_width=&#8221;0&#8243; mobile_width=&#8221;0&#8243; width=&#8221;1\/1&#8243;][vc_column_text]<\/p>\n<h1><span class=\"light-yellow\">Ecological risks<\/span><\/h1>\n<p>[\/vc_column_text][\/vc_column][\/vc_row][vc_row row_height_percent=&#8221;0&#8243; override_padding=&#8221;yes&#8221; h_padding=&#8221;7&#8243; top_padding=&#8221;4&#8243; bottom_padding=&#8221;2&#8243; overlay_alpha=&#8221;50&#8243; gutter_size=&#8221;3&#8243; column_width_percent=&#8221;100&#8243; shift_y=&#8221;0&#8243; z_index=&#8221;0&#8243;][vc_column column_width_percent=&#8221;100&#8243; gutter_size=&#8221;3&#8243; overlay_alpha=&#8221;50&#8243; shift_x=&#8221;0&#8243; shift_y=&#8221;0&#8243; shift_y_down=&#8221;0&#8243; z_index=&#8221;0&#8243; medium_width=&#8221;0&#8243; mobile_width=&#8221;0&#8243; width=&#8221;1\/1&#8243;][vc_column_text]<\/p>\n<p align=\"JUSTIFY\"><span style=\"color: #000000;\"><span lang=\"en-US\">Gene Drives are at an early stage of development. The discussion about possible consequences and risks is therefore still largely speculative. However, numerous critical points are already emerging that must be taken into account before a possible release.<\/span><\/span><\/p>\n<p>[\/vc_column_text][\/vc_column][\/vc_row][vc_row row_height_percent=&#8221;0&#8243; override_padding=&#8221;yes&#8221; h_padding=&#8221;7&#8243; top_padding=&#8221;2&#8243; bottom_padding=&#8221;0&#8243; overlay_alpha=&#8221;50&#8243; gutter_size=&#8221;4&#8243; column_width_percent=&#8221;100&#8243; shift_y=&#8221;0&#8243; z_index=&#8221;0&#8243;][vc_column column_width_percent=&#8221;100&#8243; gutter_size=&#8221;3&#8243; overlay_alpha=&#8221;50&#8243; shift_x=&#8221;0&#8243; shift_y=&#8221;0&#8243; shift_y_down=&#8221;0&#8243; z_index=&#8221;0&#8243; medium_width=&#8221;0&#8243; mobile_width=&#8221;0&#8243; width=&#8221;1\/1&#8243;][vc_column_text]<\/p>\n<h3 align=\"JUSTIFY\"><strong>Uncontrollability<\/strong><\/h3>\n<p align=\"JUSTIFY\"><span style=\"color: #000000;\"><span lang=\"en-US\">Once released into the wild, a gene drive organism actively spreads in free-living populations and can spread rapidly over large distances. <!-- Highlight if necessary -->The vast diversity of natural habitats and ecosystems affected will make the prediction and control of potential risks massively more difficult.<\/span><\/span><\/p>\n<p>[\/vc_column_text][vc_accordion active_tab=&#8221;0&#8243;][vc_accordion_tab title=&#8221;Read more&#8221; tab_id=&#8221;1585667455-1-241593424377049&#8243;][vc_column_text]<\/p>\n<p align=\"JUSTIFY\"><span style=\"color: #000000;\"><span lang=\"en-US\">In 2016, the U.S. Academy of Sciences recommended that gene drive organisms first be tested on small and remote islands.\u00b9 <\/span><\/span><span style=\"color: #000000;\"><span lang=\"en-US\">However, calculations using models show that this form of testing would not be sufficiently isolated: individual GDOs can reach other regions through water, wind or unintentional transport and <\/span><\/span><span lang=\"en-US\">spread the <\/span><span style=\"color: #000000;\"><span lang=\"en-US\">gene drive <\/span><\/span><span lang=\"en-US\">further.\u00b2 <\/span><span style=\"color: #000000;\"><span lang=\"en-US\">Moreover, GDO could be spread deliberately. <\/span><\/span><\/p>\n<p><span style=\"color: #000000;\"><span lang=\"en-US\">A group of researchers led by gene drive developer Kevin Esvelt at <\/span><\/span><span lang=\"en-US\">the <\/span><span style=\"color: #000000;\"><span lang=\"en-US\">Massachusetts Institute of Technology (MIT) in Boston<\/span><\/span><span lang=\"en-US\">, <\/span><span style=\"color: #000000;\"><span lang=\"en-US\">USA<\/span><\/span><span lang=\"en-US\">, is <\/span><span style=\"color: #000000;\"><span lang=\"en-US\">working on a gene drive variant that can be limited in its spatial spread. They call this gene drive Daisy Chain Drive.\u00b3 <\/span><\/span><span style=\"color: #000000;\"><span lang=\"en-US\">So far, however, this gene drive variant exists only in theory<\/span><\/span><span lang=\"en-US\">.<\/span><a class=\"sdendnotesym\" href=\"#sdendnote1anc\" name=\"sdendnote1sym\"><\/a>[\/vc_column_text][\/vc_accordion_tab][\/vc_accordion][\/vc_column][\/vc_row][vc_row row_height_percent=&#8221;0&#8243; override_padding=&#8221;yes&#8221; h_padding=&#8221;7&#8243; top_padding=&#8221;3&#8243; bottom_padding=&#8221;0&#8243; overlay_alpha=&#8221;50&#8243; gutter_size=&#8221;4&#8243; column_width_percent=&#8221;100&#8243; shift_y=&#8221;0&#8243; z_index=&#8221;0&#8243;][vc_column column_width_percent=&#8221;100&#8243; gutter_size=&#8221;3&#8243; overlay_alpha=&#8221;50&#8243; shift_x=&#8221;0&#8243; shift_y=&#8221;0&#8243; shift_y_down=&#8221;0&#8243; z_index=&#8221;0&#8243; medium_width=&#8221;0&#8243; mobile_width=&#8221;0&#8243; width=&#8221;1\/1&#8243;][vc_column_text]<\/p>\n<h3><strong>Irreversibility<\/strong><\/h3>\n<p align=\"JUSTIFY\"><span style=\"color: #000000;\"><span lang=\"en-US\">A gene drive causes a permanent genetic modification of the genetic material, which is passedon to all subsequent generations. Even if a gene drive encounters resistance and no longer spreads under its own power, these changes could continue to be inherited according to Mendelian rules and <\/span><\/span><span lang=\"en-US\">persist for a <\/span><span style=\"color: #000000;\"><span lang=\"en-US\">long time in the genome of the population. Only if the deactivated gene drive severely impairs the survivability of the individuals do the mechanisms of natural selection take effect, which could eliminate the change in the natural populations again.<\/span><\/span><\/p>\n<p>[\/vc_column_text][vc_accordion active_tab=&#8221;0&#8243;][vc_accordion_tab title=&#8221;Read more&#8221; tab_id=&#8221;1585811499-1-511593424377186&#8243;][vc_column_text]<\/p>\n<p align=\"JUSTIFY\"><span style=\"color: #000000;\"><span lang=\"en-US\">As early as 2014, <\/span><\/span><span lang=\"en-US\">a <\/span><span style=\"color: #000000;\"><span lang=\"en-US\">discussion started about the need for a so-called Reversal Drive, which isintended to reverse the changes of a Gene Drive in the manipulated populations. In principle, this is a modified version of the original gene drive that overwrites the genetic manipulations and prevents their further spread. However, even such a Reversal Drive could not restore the original genetic state of the population, but only introduce further genetic modifications into the genome of these populations.<\/span><\/span><\/p>\n<p><span lang=\"en-US\">In a study on fruit flies, genetic elements were presented that are designed to switch off or completely remove CRISPR\/Cas-based gene drives from the genome. Specific signposts of the CRISPR\/Cas9 gene scissors are used to terminate the chain reaction of a CRISPR\/Cas-based gene drive. The result: the gene \u2018scissors\u2019 paralyze themselves. Results from cage experiments show that these elements have prevailed after 10 generations. However, synthetic genetic elements remain in the genome and are inherited according to Mendelian rules. In addition, unintended changes to the genome occur. It is difficult to estimate how these remaining genetic changes will behave in the wild populations in the long term and whether they will be influenced by external factors.<sup>4 <\/sup><\/span><span style=\"color: #000000;\"><span lang=\"en-US\">According to current knowledge, any release of a gene drive carries the risk of irreversibly and uncontrollably altering the genetic material of a natural population.<sup>5<\/sup><!-- highlight --><\/span><\/span><a class=\"sdendnotesym\" href=\"#sdendnote1anc\" name=\"sdendnote1sym\"><\/a>[\/vc_column_text][\/vc_accordion_tab][\/vc_accordion][\/vc_column][\/vc_row][vc_row row_height_percent=&#8221;0&#8243; override_padding=&#8221;yes&#8221; h_padding=&#8221;7&#8243; top_padding=&#8221;3&#8243; bottom_padding=&#8221;0&#8243; overlay_alpha=&#8221;50&#8243; gutter_size=&#8221;4&#8243; column_width_percent=&#8221;100&#8243; shift_y=&#8221;0&#8243; z_index=&#8221;0&#8243;][vc_column column_width_percent=&#8221;100&#8243; gutter_size=&#8221;3&#8243; overlay_alpha=&#8221;50&#8243; shift_x=&#8221;0&#8243; shift_y=&#8221;0&#8243; shift_y_down=&#8221;0&#8243; z_index=&#8221;0&#8243; medium_width=&#8221;0&#8243; mobile_width=&#8221;0&#8243; width=&#8221;1\/1&#8243;][vc_column_text]<\/p>\n<h3><strong>Outcrossing across species boundaries<\/strong><\/h3>\n<p align=\"JUSTIFY\"><span style=\"color: #000000;\"><span lang=\"en-US\">Gene drives are tailored to the genome of a single species, but in many cases outcrossing across species boundaries could be inevitable<!-- Highlight if necessary -->. <\/span><\/span><\/p>\n<p>[\/vc_column_text][vc_accordion active_tab=&#8221;0&#8243;][vc_accordion_tab title=&#8221;Read more&#8221; tab_id=&#8221;1585811780-1-21593424377367&#8243;][vc_column_text]<\/p>\n<p align=\"JUSTIFY\"><span style=\"color: #000000;\"><span lang=\"en-US\">For example, the malaria-carrying mosquito Anopheles gambiae belongs to a complex of seven different subspecies that are genetically very similar and can produce fertile offspring with each other.<sup>6<\/sup> <\/span><\/span><span style=\"color: #000000;\"><span lang=\"en-US\">A gene drive by Target Malaria targets disruption of the gene Doublesex, which has undergone little change during the evolution of the mosquito species. This approach could drive all seven related mosquito species to the brink of extinction, although at least one species does not transmit malaria.<sup>7<\/sup><!-- What should be the statement? --><\/span><\/span><\/p>\n<p align=\"JUSTIFY\"><span style=\"color: #000000;\"><span lang=\"en-US\">A similar risk exists in fruit flies of the genus Drosophila, which have played a central role in the development and <\/span><\/span><span lang=\"en-US\">application of <\/span><span style=\"color: #000000;\"><span lang=\"en-US\">gene drives. It has been known for over 90 years that different species of Drosophila can interbreed and produce fertile offspring.<sup>8 <\/sup><\/span><\/span><span style=\"color: #000000;\"><span lang=\"en-US\">Thousands of other animal and plant species form natural hybrids, so the spread of gene drives would not be limited to one species but could also extend to its closer relatives.<\/span><\/span><\/p>\n<div id=\"sdendnote1\">\n<p><a class=\"sdendnotesym\" href=\"#sdendnote1anc\" name=\"sdendnote1sym\"><\/a><\/p>\n<\/div>\n<p>[\/vc_column_text][\/vc_accordion_tab][\/vc_accordion][\/vc_column][\/vc_row][vc_row row_height_percent=&#8221;0&#8243; override_padding=&#8221;yes&#8221; h_padding=&#8221;7&#8243; top_padding=&#8221;3&#8243; bottom_padding=&#8221;0&#8243; overlay_alpha=&#8221;50&#8243; gutter_size=&#8221;4&#8243; column_width_percent=&#8221;100&#8243; shift_y=&#8221;0&#8243; z_index=&#8221;0&#8243;][vc_column column_width_percent=&#8221;100&#8243; gutter_size=&#8221;3&#8243; overlay_alpha=&#8221;50&#8243; shift_x=&#8221;0&#8243; shift_y=&#8221;0&#8243; shift_y_down=&#8221;0&#8243; z_index=&#8221;0&#8243; medium_width=&#8221;0&#8243; mobile_width=&#8221;0&#8243; width=&#8221;1\/1&#8243;][vc_column_text]<\/p>\n<h3><strong>Unexpected effects of CRISPR\/Cas9<\/strong><\/h3>\n<p><span style=\"color: #000000;\"><span lang=\"en-US\">Many engineered gene drives use CRISPR\/Cas9 to create a double-strand break at defined locations in the genome. However, this tool does not work flawlessly.<sup>9 <\/sup><\/span><\/span><span style=\"color: #000000;\"><span lang=\"en-US\">CRISPR\/Cas9 can change the activity of the target gene in unpredictable ways, increase the mutation rate in the genome<\/span><\/span><span style=\"color: #000000;\"><span lang=\"en-US\">,<\/span><\/span><span style=\"color: #000000;\"><span lang=\"en-US\"> lead to unexpected mutations, or be disrupted in its function by emerging resistances. For example, there are increasing reports of so-called off-target effects, unintended changes to non-target sequences that can occur when the CRISPR\/Cas system is applied.<sup>10<\/sup><\/span><\/span><a class=\"sdendnotesym\" href=\"#sdendnote1anc\" name=\"sdendnote1sym\"><\/a>[\/vc_column_text][vc_accordion active_tab=&#8221;0&#8243;][vc_accordion_tab title=&#8221;Read more&#8221; tab_id=&#8221;1585812246-1-251593424377573&#8243;][vc_column_text]<span style=\"color: #000000;\"><span lang=\"en-US\">Moreover, the genetic modifications not only affect the target area, but often also other areas in the genome.<sup>11 <\/sup><\/span><\/span><span style=\"color: #000000;\"><span lang=\"en-US\">One of the reasons for this is that in wild populations there are more sequences in the genome to which CRISPR\/Cas9 can dock than the computer programs used for this purpose were able to determine in the laboratory. Gene drives can therefore lead to the development of organisms with unpredictable characteristics.<sup>12<\/sup><\/span><\/span><a class=\"sdendnotesym\" href=\"#sdendnote1anc\" name=\"sdendnote1sym\"><\/a>[\/vc_column_text][\/vc_accordion_tab][\/vc_accordion][\/vc_column][\/vc_row][vc_row row_height_percent=&#8221;0&#8243; override_padding=&#8221;yes&#8221; h_padding=&#8221;7&#8243; top_padding=&#8221;3&#8243; bottom_padding=&#8221;0&#8243; overlay_alpha=&#8221;50&#8243; gutter_size=&#8221;4&#8243; column_width_percent=&#8221;100&#8243; shift_y=&#8221;0&#8243; z_index=&#8221;0&#8243;][vc_column column_width_percent=&#8221;100&#8243; gutter_size=&#8221;3&#8243; overlay_alpha=&#8221;50&#8243; shift_x=&#8221;0&#8243; shift_y=&#8221;0&#8243; shift_y_down=&#8221;0&#8243; z_index=&#8221;0&#8243; medium_width=&#8221;0&#8243; mobile_width=&#8221;0&#8243; width=&#8221;1\/1&#8243;][vc_column_text]<\/p>\n<h3><strong>Resistances<\/strong><\/h3>\n<p align=\"JUSTIFY\"><span style=\"color: #000000;\"><span lang=\"en-US\">CRISPR\/Cas-based gene drives search for a clearly defined DNA sequence at which they are to cut the genetic material. Even single mutations to this sequence can therefore render the target unrecognizable to them. The organism thus becomes resistant to the gene drive. Such resistance can arise if the DNA double-strand break generated by CRISPR\/Cas9 is incorrectly repaired by the cell and alters the target sequence<\/span><\/span><span lang=\"en-US\">. However, resistance could also occur naturally, <\/span><span style=\"color: #000000;\"><span lang=\"en-US\">especially in populations with high genetic diversity.<\/span><\/span><\/p>\n<p>[\/vc_column_text][vc_accordion active_tab=&#8221;0&#8243;][vc_accordion_tab title=&#8221;Read more&#8221; tab_id=&#8221;1585818319-1-741593424377800&#8243;][vc_column_text]<\/p>\n<p align=\"JUSTIFY\"><span style=\"color: #000000;\"><span lang=\"en-US\">If a gene drive encounters resistance, it will break off at this point and only change part of the population. Whether it disappears again completely, however, depends on the number of individuals already changed and the disadvantages that the gene drive brings for their survival. It is therefore entirely possible for the gene drive to persist for a long time in an animal species despite resistance.<\/span><\/span><\/p>\n<p>[\/vc_column_text][\/vc_accordion_tab][\/vc_accordion][\/vc_column][\/vc_row][vc_row row_height_percent=&#8221;0&#8243; override_padding=&#8221;yes&#8221; h_padding=&#8221;7&#8243; top_padding=&#8221;3&#8243; bottom_padding=&#8221;0&#8243; overlay_alpha=&#8221;50&#8243; gutter_size=&#8221;4&#8243; column_width_percent=&#8221;100&#8243; shift_y=&#8221;0&#8243; z_index=&#8221;0&#8243;][vc_column column_width_percent=&#8221;100&#8243; gutter_size=&#8221;3&#8243; overlay_alpha=&#8221;50&#8243; shift_x=&#8221;0&#8243; shift_y=&#8221;0&#8243; shift_y_down=&#8221;0&#8243; z_index=&#8221;0&#8243; medium_width=&#8221;0&#8243; mobile_width=&#8221;0&#8243; width=&#8221;1\/1&#8243;][vc_column_text]<\/p>\n<h3><strong>Unpredictable effects on ecosystems <\/strong><\/h3>\n<p align=\"JUSTIFY\"><span style=\"color: #000000;\"><span lang=\"en-US\">Every living creature, even if it appears dangerous or harmful to <\/span><\/span><span lang=\"en-US\">humans<\/span><span style=\"color: #000000;\"><span lang=\"en-US\">, performs important tasks in its habitat. The extinction or even manipulation of one species will therefore have consequences for the entire ecosystem. <\/span><\/span><\/p>\n<p>[\/vc_column_text][vc_accordion active_tab=&#8221;0&#8243;][vc_accordion_tab title=&#8221;Read more&#8221; tab_id=&#8221;1585989181-1-241593424378068&#8243;][vc_column_text]<\/p>\n<p align=\"JUSTIFY\"><span style=\"color: #000000;\"><span lang=\"en-US\">This can be well illustrated by the example of mosquitoes. In the course of their life cycle, <\/span><\/span><span lang=\"en-US\">they <\/span><span style=\"color: #000000;\"><span lang=\"en-US\">form important food sources for various animals. For example, mosquito larvae living in water are a food source for water bugs, beetles, flies, spiders, flatworms, tadpoles, fish and crustaceans. It is assumed that 95 percent of the larvae of the African malaria mosquito Anopheles gambiae are being eaten before becoming adults.<sup>13<\/sup><\/span><\/span><span style=\"color: #000000;\"><span lang=\"en-US\"> Adult mosquitoes are also an important food source and are consumed by dragonflies, spiders, bats and birds, among others. In the Camargue, a nature reserve in southern France, decimation of mosquitoes with a biological control agent has also led to a reduction in the number and diversity of birds and dragonflies.<sup>14 <\/sup><\/span><\/span><span style=\"color: #000000;\"><span lang=\"en-US\">A role in plant pollination also cannot be ruled out, as adult mosquitoes feed on nectar, among other things.<sup>15<\/sup><\/span><\/span><span style=\"color: #000000;\"><span lang=\"en-US\"> The role of mosquitoes in their tightly interwoven ecosystem has hardly been studied so far, so the consequences of a possible extinction are not foreseeable. <\/span><\/span><\/p>\n<p align=\"JUSTIFY\"><span lang=\"en-US\">These consequences can also affect humans: If one mosquito species is displaced, other species, which may transmit even more dangerous diseases, can spread more widely. Such risk scenarios are known with regard to the control of the dengue fever-transmitting yellow fever mosquito (Aedes aegypti) in North America and Brazil, which competes with the invasive <\/span><span lang=\"en-US\">Asian tiger mosquito (Aedes albopictus).<sup>16<\/sup><\/span> <span lang=\"en-US\">If the yellow fever mosquito disappears, this could further promote the spread of the tiger mosquito, which is no less dangerous and also transmits dengue fever.<sup>17<\/sup><\/span><\/p>\n<p align=\"JUSTIFY\"><span lang=\"en-US\">But even if a species is not wiped out, gene drives harbor considerable risks: If the characteristics of the organisms change unintentionally, they can, for example, become more vital, change their behavior, transmit more diseases, or even disturb or destroy the habitat of other species. Because the respective species are closely linked to their ecosystems, the effects of uncontrolled spreads cannot be predicted reliably.<sup>18<\/sup><\/span><\/p>\n<p>[\/vc_column_text][vc_single_image media=&#8221;1451&#8243; media_lightbox=&#8221;yes&#8221; media_width_percent=&#8221;100&#8243;][\/vc_accordion_tab][\/vc_accordion][\/vc_column][\/vc_row][vc_row row_height_percent=&#8221;0&#8243; override_padding=&#8221;yes&#8221; h_padding=&#8221;7&#8243; top_padding=&#8221;3&#8243; bottom_padding=&#8221;4&#8243; overlay_alpha=&#8221;50&#8243; gutter_size=&#8221;4&#8243; column_width_percent=&#8221;100&#8243; shift_y=&#8221;0&#8243; z_index=&#8221;0&#8243;][vc_column column_width_percent=&#8221;100&#8243; gutter_size=&#8221;3&#8243; overlay_alpha=&#8221;50&#8243; shift_x=&#8221;0&#8243; shift_y=&#8221;0&#8243; shift_y_down=&#8221;0&#8243; z_index=&#8221;0&#8243; medium_width=&#8221;0&#8243; mobile_width=&#8221;0&#8243; width=&#8221;1\/1&#8243;][vc_accordion active_tab=&#8221;0&#8243;][vc_accordion_tab title=&#8221;References&#8221; tab_id=&#8221;1585818202-1-141593424378353&#8243;][vc_column_text]<\/p>\n<div id=\"sdendnote1\">\n<ol>\n<li><span lang=\"en-US\">National Academies of Science, Engineering and Medicine (2016). Gene Drives on the Horizon: <\/span><span lang=\"en-US\">Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values. Washington, DC: The National Academies Press<\/span><\/li>\n<li><span lang=\"en-US\">Noble C, Adlam B, Church GM, Esvelt KM, Nowak MA (2017). Current CRISPR gene drive systems are likely to be highly invasive in wild populations. Elife 7:e33423<\/span><\/li>\n<li><span lang=\"en-US\">Noble C, Min J, Olejarz <\/span><span lang=\"en-US\">J, <\/span><span lang=\"en-US\">Buchthal J, Chavez A, Smidler AL, DeBenedictis EA, Church GM, Nowak MA, Esvelt KM (2019). Daisy-chain gene drives for the alteration of local populations. Proc Natl Acad Sci USA 116:8275<\/span><\/li>\n<li><span lang=\"en-US\">Xu X-RS, Bulger EA, Gantz VM, Klanseck C, Heimler SR, Auradkar A, Bennett JB, Miller LA, Leahy S, Juste SS, Buchman A, Akbari OS, Marshall JM, Bier E (2020) Active Genetic Neutralizing Elements for Halting or Deleting Gene Drives. 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Genetics 186:1<\/span><\/li>\n<li><span lang=\"en-US\">Kosicki M, Tomberg K, Bradley A (2018). Repair of double-strand breaks induced by CRISPR-Cas9 leads to large deletions and complex rearrangements. Nat Biotechnol 36:765<\/span><\/li>\n<li><span lang=\"en-US\">Kawall K, Cotter J, Then C (2020). Broadening the GMO risk assessment in the EU for genome editing technologies in agriculture. Environ Sci Eur. 32(1):201<\/span><\/li>\n<li><span lang=\"en-US\">Fu Y, Foden JA, Khayter C, Maeder ML, Reyon D, Joung JK, Sander JD (2013). High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat Biotechnol 31:822<\/span><\/li>\n<li><span lang=\"en-US\">Lindholm AK, Dyer KA, Firman RC, Fishman L, Forstmeier W, Holman L, Johannesson H, Knief U, Kokko H, Larracuente AM, Manser A, Montchamp-Moreau C, Petrosyan VG, Pomiankowski A, Presgraves DC, Safronova LD, Sutter A, Unckless RL, Verspoor RL, Wedell T (2016). The Ecology and Evolutionary Dynamics of Meiotic Drive. 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