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| − | {{concept
| + | #REDIRECT[[Genetic Extinction Technology]] |
| − | |wikipedia=https://en.wikipedia.org/wiki/Gene_drive
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| − | |interest_of=Bill & Melinda Gates Foundation, Moderna
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| − | [[File:Gene Drive.png|thumb|485x485px]]
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| − | A '''gene drive''' is a natural process<ref>>{{Cite journal|last1=Alphey|first1=Luke S.|last2=Crisanti|first2=Andrea|last3=Randazzo|first3=Filippo (Fil)|last4=Akbari|first4=Omar S.|date=2020-11-18|title=Opinion: Standardizing the definition of gene drive|url=https://www.pnas.org/content/early/2020/11/10/2020417117|journal=Proceedings of the National Academy of Sciences|language=en|doi=10.1073/pnas.2020417117|issn=0027-8424|pmid=33208534</ref> and technology of [[genetic engineering]] that propagates a particular suite of genes throughout a population<ref>>https://www.nature.com/news/us-defence-agencies-grapple-with-gene-drives-1.22345</ref> by altering the probability that a specific allele will be transmitted to offspring (instead of the [[Mendelian inheritance|Mendelian 50%]] probability).
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| − | The U.S. [[Defense Advanced Research Projects Agency]] (DARPA) has given approximately $100 million for gene drive research, making them likely the largest single funder of gene drive research on the planet. The secretive top-level [[JASON group]] of military advisors produced a [[classified]] study on gene drive in 2017, reflecting an extremely high level of interest and activity by other sections of the U.S. military and Intelligence community<reF>http://genedrivefiles.synbiowatch.org/2017/12/01/us-military-gene-drive-development/</ref>.
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| − | The [[Bill and Melinda Gates Foundation]] paid a PR firm $1.6 million to secretly stack key UN advisory processes with gene drive-friendly scientists, and recruited ostensibly independent academics and public officials into a private collaboration to counteract proposed regulations and to resist calls by scientists and conservationists for an international moratorium<ref>https://etcgroup.org/content/gene-drive-files</ref>.
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| − | Gene drives can arise through a variety of mechanisms.<ref>>{{cite journal | vauthors = Champer J, Buchman A, Akbari OS | title = Cheating evolution: engineering gene drives to manipulate the fate of wild populations | journal = Nature Reviews. Genetics | volume = 17 | issue = 3 | pages = 146–59 | date = March 2016 | pmid = 26875679 | doi = 10.1038/nrg.2015.34 | doi-access = free </ref><ref>>{{cite journal | vauthors = Leftwich PT, Edgington MP, Harvey-Samuel T, Carabajal Paladino LZ, Norman VC, Alphey L | title = Recent advances in threshold-dependent gene drives for mosquitoes | journal = Biochemical Society Transactions | volume = 46 | issue = 5 | pages = 1203–1212 | date = October 2018 | pmid = 30190331 | pmc = 6195636 | doi = 10.1042/BST20180076 </ref> They have been proposed to provide an effective means of genetically modifying specific populations and entire species.
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| − | The technique can employ adding, deleting, disrupting, or modifying genes.<ref> name="el14072"</ref><ref> name="rspb14072">{{cite journal | vauthors = Burt A | title = Site-specific selfish genes as tools for the control and genetic engineering of natural populations | journal = Proceedings. Biological Sciences | volume = 270 | issue = 1518 | pages = 921–8 | date = May 2003 | pmid = 12803906 | pmc = 1691325 | doi = 10.1098/rspb.2002.2319 </ref>
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| − | Proposed applications include exterminating insects that carry pathogens (notably mosquitoes that transmit [[malaria]], [[dengue]], and [[Zika fever|zika]] pathogens), controlling [[invasive species]], or eliminating [[herbicide]] or [[pesticide resistance]].<ref> name="sm1407">|url=http://news.sciencemag.org/biology/2014/07/u-s-researchers-call-greater-oversight-powerful-genetic-technology|title=U.S. researchers call for greater oversight of powerful genetic technology | Science/AAAS | News|date=|publisher=News.sciencemag.org|access-date=2014-07-18</ref><ref> name="el14072">{{cite journal | vauthors = Esvelt KM, Smidler AL, Catteruccia F, Church GM | title = Concerning RNA-guided gene drives for the alteration of wild populations | journal = eLife | volume = 3 | pages = e03401 | date = July 2014 | pmid = 25035423 | pmc = 4117217 | doi = 10.7554/eLife.03401 | authorlink1 = Kevin M. Esvelt | authorlink3 = Flaminia Catteruccia </ref><ref>>{{cite journal | vauthors = Benedict M, D'Abbs P, Dobson S, Gottlieb M, Harrington L, Higgs S, James A, James S, Knols B, Lavery J, O'Neill S, Scott T, Takken W, Toure Y | display-authors = 6 | title = Guidance for contained field trials of vector mosquitoes engineered to contain a gene drive system: recommendations of a scientific working group | journal = Vector Borne and Zoonotic Diseases | volume = 8 | issue = 2 | pages = 127–66 | date = April 2008 | pmid = 18452399 | doi = 10.1089/vbz.2007.0273 | doi-access = free </ref><ref>>{{Cite book | last1=Redford |first1=Kent H. |last2=Brooks |first2=Thomas M. |last3=Macfarlane |first3=Nicholas B. W. |last4=Adams |first4=Jonathan S | name-list-style = vanc |url=https://portals.iucn.org/library/node/48408 |title=Genetic frontiers for conservation...technical assessment. |date=2019|isbn=978-2-8317-1974-0|language=en|doi=10.2305/iucn.ch.2019.05.en</ref>
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| − | As with any potentially powerful technique, gene drives can be misused in a variety of ways or induce unintended consequences. For example, a gene drive intended to affect only a local population might spread across an entire species. Gene drives used to eradicate populations of invasive species in their non-native habitats may have consequences for the population of the species as a whole, even in its native habitat. Any accidental return of individuals of the species to its original habitats, through natural migration, environmental disruption (storms, floods, etc.), accidental human transportation, or purposeful relocation, could unintentionally drive the species to extinction if the relocated individuals carried harmful gene drives.<ref>> | url = https://www.wired.com/story/this-gene-editing-tech-might-be-too-dangerous-to-unleash/ | title = This Gene-Editing Tech Might Be Too Dangerous To Unleash | work = Wired </ref>
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| − | Gene drives can be built from many naturally occurring [[selfish genetic elements]] that use a variety of molecular mechanisms.<ref> name=":1">{{cite journal | vauthors = Champer J, Buchman A, Akbari OS | title = Cheating evolution: engineering gene drives to manipulate the fate of wild populations | journal = Nature Reviews. Genetics | volume = 17 | issue = 3 | pages = 146–59 | date = March 2016 | pmid = 26875679 | doi = 10.1038/nrg.2015.34 | doi-access = free </ref> These naturally occurring mechanisms induce similar [[segregation distortion]] in the wild, arising when [[allele]]s evolve molecular mechanisms that give them a transmission chance greater than the normal 50%.
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| − | Most gene drives have been developed in insects, notably mosquitoes, as a way to control insect-borne pathogens. Recent developments designed gene drives directly in viruses, notably [[Herpesviridae|herpesviruses]]. These viral gene drives can propagate a modification into the population of viruses, and aim to reduce the infectivity of the virus.<ref> name=":2">{{Cite journal|last1=Walter|first1=Marius|last2=Verdin|first2=Eric|date=2020-09-28|title=Viral gene drive in herpesviruses|url=https://www.nature.com/articles/s41467-020-18678-0|journal=Nature Communications|language=en|volume=11|issue=1|pages=4884|doi=10.1038/s41467-020-18678-0|pmid=32985507|pmc=7522973|issn=2041-1723</ref><ref>>|date=2020-09-30|title=Gene Drives Could Kill Mosquitoes and Suppress Herpesvirus Infections|url=https://www.acsh.org/news/2020/09/30/gene-drives-could-kill-mosquitoes-and-suppress-herpesvirus-infections-15060|access-date=2020-10-07|website=American Council on Science and Health|language=en</ref>
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| − | == Mechanism ==
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| − | In [[Sexual reproduction|sexually-reproducing]] species, most genes are present in two copies (which can be the same or different [[allele]]s), either one of which has a 50% chance of passing to a descendant. By biasing the inheritance of particular altered genes, synthetic gene drives could spread alterations through a population.<ref> name="el14072"</ref><ref> name="rspb14072"</ref >
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| − | === Molecular mechanisms ===
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| − | [[File:Molecular mechanism of gene drive.svg|alt=Molecular mechanism of gene drive.|thumb|540x540px|Molecular mechanism of gene drive.]]
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| − | At the molecular level, an endonuclease gene drive works by cutting a [[chromosome]] at a specific site that does not encode the drive, inducing the cell to [[DNA repair|repair the damage]] by copying the drive sequence onto the damaged chromosome. The cell then has two copies of the drive sequence. The method derives from [[genome editing]] techniques and relies on the fact that double strand breaks are most frequently repaired by [[homologous recombination]], (in the presence of a template), rather than [[non-homologous end joining]]. To achieve this behavior, endonuclease gene drives consist of two nested elements:
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| − | * either a [[homing endonuclease]] or a RNA-guided endonuclease (e.g., [[Cas9]] or [[CRISPR/Cpf1|Cpf1]]<ref>>{{Cite news|url=https://www.economist.com/news/science-and-technology/21668031-scientists-have-found-yet-another-way-edit-genomes-suggesting-such-technology-will|title=Even CRISPR|newspaper=The Economist|issn=0013-0613|access-date=2016-05-03</ref>) and its [[guide RNA]], that cuts the target sequence in recipient cells
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| − | * a template sequence used by the DNA repair machinery after the target sequence is cut. To achieve the self-propagating nature of gene drives, this repair template contains at least the endonuclease sequence. Because the template must be used to repair a [[double-strand break]] at the cutting site, its sides are [[Homology (biology)|homologous]] to the sequences that are adjacent to the cutting site in the host genome. By targeting the gene drive to a gene coding sequence, this gene will be inactivated; additional sequences can be introduced in the gene drive to encode new functions.
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| − | As a result, the gene drive insertion in the genome will re-occur in each organism that inherits one copy of the modification and one copy of the wild-type gene. If the gene drive is already present in the egg cell (e.g. when received from one parent), all the gametes of the individual will carry the gene drive (instead of 50% in the case of a normal gene).<ref> name="el14072"</ref>
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| − | === Spreading in the population ===
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| − | Since it can never more than double in frequency with each generation, a gene drive introduced in a single individual typically requires dozens of generations to affect a substantial fraction of a population. Alternatively, releasing drive-containing organisms in sufficient numbers can affect the rest within a few generations; for instance, by introducing it in every thousandth individual, it takes only 12–15 generations to be present in all individuals.<ref> name=":22">{{cite journal | vauthors = Unckless RL, Messer PW, Connallon T, Clark AG | title = Modeling the Manipulation of Natural Populations by the Mutagenic Chain Reaction | journal = Genetics | volume = 201 | issue = 2 | pages = 425–31 | date = October 2015 | pmid = 26232409 | pmc = 4596658 | doi = 10.1534/genetics.115.177592 </ref> Whether a gene drive will ultimately become fixed in a population and at which speed depends on its effect on individuals fitness, on the rate of allele conversion, and on the population structure. In a well mixed population and with realistic allele conversion frequencies (≈90%), population genetics predicts that gene drives get fixed for selection coefficient smaller than 0.3;<ref> name=":22" </ref> in other words, gene drives can be used to spread modifications as long as reproductive success is not reduced by more than 30%. This is in contrast with normal genes, which can only spread across large populations if they increase fitness.
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| − | === Gene drive in viruses ===
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| − | Because the strategy usually relies on the simultaneous presence of an unmodified and a gene drive allele in the same [[cell nucleus]], it had generally been assumed that a gene drive could only be engineered in sexually reproducing organisms, excluding [[bacteria]] and [[Virus|viruses]]. However, during a [[viral infection]], viruses can accumulate hundreds or thousand genome copies in infected cells. Beside, cells are frequently co-infected by multiple virions and [[Homologous recombination|recombination]] between viral genomes is a well-known and widespread source of diversity for many viruses. In particular, [[Herpesviridae|herpesviruses]] are nuclear-replicating [[DNA virus|DNA viruses]] with large double-stranded DNA genomes and frequently undergo homologous recombination during their replication cycle.
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| − | These properties have enabled the design of a gene drive strategy that doesn’t involve sexual reproduction, but relies on [[Coinfection|co-infection]] of a given cell by a naturally occurring and an engineered virus. Upon co-infection, the unmodified genome is cut and repaired by homologous recombination, producing new gene drive viruses that can progressively replace the naturally occurring population. In [[cell culture]] experiments, it was shown that a viral gene drive can spread into the viral population and strongly reduce the infectivity of the virus, which opens novel therapeutic strategies against herpesviruses.<ref> name=":2" </ref>
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| − | == Technical limitations ==
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| − | Because gene drives propagate by replacing other alleles that contain a cutting site and the corresponding homologies, their application has been mostly limited to sexually reproducing species (because they are [[Ploidy|diploid]] or [[Polyploid#Plants|polyploid]] and alleles are mixed at each generation). As a side effect, inbreeding could in principle be an escape mechanism, but the extent to which this can happen in practice is difficult to evaluate.<ref>>{{cite biorxiv|last=Bull|first=James J. | name-list-style = vanc |date=2016-04-02|title=Lethal Gene Drive Selects Escape through Inbreeding|biorxiv=10.1101/046847</ref>
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| − | Due to the number of generations required for a gene drive to affect an entire population, the time to universality varies according to the reproductive cycle of each species: it may require under a year for some invertebrates, but centuries for organisms with years-long intervals between birth and [[sexual maturity]], such as humans.<ref>>{{cite journal | vauthors = Oye KA, Esvelt K, Appleton E, Catteruccia F, Church G, Kuiken T, Lightfoot SB, McNamara J, Smidler A, Collins JP | display-authors = 6 | title = Biotechnology. Regulating gene drives | journal = Science | volume = 345 | issue = 6197 | pages = 626–8 | date = August 2014 | pmid = 25035410 | doi = 10.1126/science.1254287 | doi-access = free </ref> Hence this technology is of most use in fast-reproducing species.
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| − | == Issues ==
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| − | Issues highlighted by researchers include:<ref>> | vauthors = Drinkwater K, Kuiken T, Lightfoot S, McNamara J, Oye K | title = Creating a research agenda for the ecological implications of synthetic biology. | publisher = MIT Center for International Studies and Woodrow Wilson International Center for Scholars | location = Cambridge, MA and Washington, DC. | date = May 2014 |url=http://www.synbioproject.org/process/assets/files/6685/synbio_res_agenda1.pdf |access-date=2014-07-20|archive-url= https://web.archive.org/web/20140730041832/http://www.synbioproject.org/process/assets/files/6685/synbio_res_agenda1.pd |archive-date=2014-07-30 |url-status=dead </ref>
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| − | * Mutations: A mutation could happen mid-drive, which has the potential to allow unwanted traits to "ride along".
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| − | * Escape: Cross-breeding or [[gene flow]] potentially allow a drive to move beyond its target population.
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| − | * Ecological impacts: Even when new traits' direct impact on a target is understood, the drive may have side effects on the surroundings.
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| − | The [[Broad Institute]] of MIT and Harvard added gene drives to a list of uses of gene-editing technology it doesn't think companies should pursue.<ref> name=":4">{{Cite news|url=https://www.technologyreview.com/s/609619/farmers-seek-to-deploy-powerful-gene-drive/|title=California farmers are eyeing a controversial genetic tool to eliminate fruit flies|last=Regalado|first=Antonio | name-list-style = vanc |date=December 12, 2017|work=MIT Technology Review|access-date=2018-04-28|language=en</ref>
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| − | === Bioethics concerns ===
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| − | Gene drives affect all future generations and represent the possibility of a larger change in a living species than has been possible before.<ref>>|url=https://www.pbs.org/wgbh/nova/next/evolution/crispr-gene-drives/|title=Genetically Engineering Almost Anything|date=17 July 2014|publisher=PBS "I don't care if it's a weed or a blight, people still are going to say this is way too massive a genetic engineering project," [bioethicist] Caplan says. "Secondly, it's altering things that are inherited, and that's always been a bright line for genetic engineering."</ref>
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| − | In December 2015, scientists of major world academies called for a moratorium on inheritable [[human genome]] edits that would affect the germline, including those related to [[#CRISPR/Cas9|CRISPR-Cas9]] technologies,<ref> name="NYT-20151203-nw2">{{cite news|url=https://www.nytimes.com/2015/12/04/science/crispr-cas9-human-genome-editing-moratorium.html|title=Scientists Place Moratorium on Edits to Human Genome That Could Be Inherited|last=Wade|first=Nicholas| name-list-style = vanc |date=3 December 2015|work=[[The New York Times]] |authorlink=Nicholas Wade|access-date=3 December 2015</ref> but supported continued basic research and gene editing that would not affect future generations.<ref> name="NewScientist201512092">{{cite news|url=https://www.newscientist.com/article/mg22830514-500-geneticists-vote-to-allow-gene-editing-of-human-embryos/|title=Geneticists vote to allow gene editing of human embryos|date=9 December 2015|publisher=New Scientist|last1=Huffaker|first1=Sandy| name-list-style = vanc |access-date=18 March 2016</ref> In February 2016, British scientists were given permission by regulators to genetically modify [[human embryos]] by using CRISPR-Cas9 and related techniques on condition that the embryos were destroyed in seven days.<ref> name="BBC-201602012">{{cite news|url=https://www.bbc.co.uk/news/health-35459054|title=Scientists get 'gene editing' go-ahead|last=Gallagher|first=James| name-list-style = vanc |date=1 February 2016|work=[[BBC News]] |access-date=1 February 2016</ref><ref> name="AP-201602012">{{cite news|url=http://bigstory.ap.org/article/fdda5bf9f0314b748c7438c9659da83a/britain-approves-controversial-gene-editing-technique |title=Britain approves controversial gene-editing technique |last=Cheng |first=Maria | name-list-style = vanc |date=1 February 2016 |publisher=[[Associated Press]] |access-date=1 February 2016 |url-status=dead |archive-url=https://web.archive.org/web/20160201114343/http://bigstory.ap.org/article/fdda5bf9f0314b748c7438c9659da83a/britain-approves-controversial-gene-editing-technique |archive-date=1 February 2016</ref> In June 2016, the US [[National Academies of Sciences, Engineering, and Medicine]] released a report on their "Recommendations for Responsible Conduct" of gene drives.<ref>>|url=http://nas-sites.org/gene-drives/|title=Gene Drive Research in Non-Human Organisms: Recommendations for Responsible Conduct|work=National Academies of Sciences, Engineering, and Medicine|date=June 8, 2016|access-date=June 9, 2016</ref>
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| − | Models suggest that extinction-oriented gene drives will wipe out target species and that drives could reach populations beyond the target given minimal connectivity between them.<ref>>{{cite journal | vauthors = Noble C, Adlam B, Church GM, Esvelt KM, Nowak MA | title = Current CRISPR gene drive systems are likely to be highly invasive in wild populations | journal = eLife | volume = 7 | date = June 2018 | pmid = 29916367 | doi = 10.7554/eLife.33423 | pmc = 6014726 </ref>
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| − | [[Kevin M. Esvelt]] stated that an open conversation was needed around the safety of gene drives: "In our view, it is wise to assume that invasive and self-propagating gene drive systems are likely to spread to every population of the target species throughout the world. Accordingly, they should only be built to combat true plagues such as malaria, for which we have few adequate countermeasures and that offer a realistic path towards an international agreement to deploy among all affected nations.".<ref>>{{cite journal | vauthors = Esvelt KM, Gemmell NJ | title = Conservation demands safe gene drive | journal = PLOS Biology | volume = 15 | issue = 11 | pages = e2003850 | date = November 2017 | pmid = 29145398 | pmc = 5689824 | doi = 10.1371/journal.pbio.2003850 </ref> He moved to an open model for his own research on using gene drive to eradicate [[Lyme disease]] in [[Nantucket]] and [[Martha's Vineyard]].<ref>>|last1=Yong|first1=Ed| name-list-style = vanc |title=One Man's Plan to Make Sure Gene Editing Doesn't Go Haywire|url=https://www.theatlantic.com/science/archive/2017/07/a-scientists-plan-to-protect-the-world-by-changing-how-science-is-done/532962/|website=theatlantic.com|access-date=13 December 2017</ref> Esvelt and colleagues suggested that CRISPR could be used to save endangered wildlife from extinction. Esvelt later retracted his support for the idea, except for extremely hazardous populations such as malaria-carrying mosquitoes and isolated islands that would prevent the drive from spreading beyond the target area.<ref>>{{Cite news|url=https://www.nytimes.com/2017/11/16/science/gene-drives-crispr.html|title='Gene Drives' Are Too Risky for Field Trials, Scientists Say|last=Zimmer|first=Carl | name-list-style = vanc |date=2017-11-16|work=The New York Times|access-date=2018-04-22|language=en-US|issn=0362-4331</ref>
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| − | == History ==
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| − | Austin Burt, an [[Extended evolutionary synthesis|evolutionary geneticist]] at [[Imperial College London]], introduced the possibility of conducting gene drives based on natural homing endonuclease [[selfish genetic elements]] in 2003.<ref> name="rspb14072"</ref>
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| − | Researchers had already shown that such genes could [[Gene-centered view of evolution#Selfish-gene theory|act selfishly]] to spread rapidly over successive generations. Burt suggested that gene drives might be used to prevent a mosquito population from transmitting the [[malaria parasite]] or to crash a mosquito population. Gene drives based on homing endonucleases have been demonstrated in the laboratory in [[transgenic]] populations of mosquitoes<ref>>{{cite journal | vauthors = Windbichler N, Menichelli M, Papathanos PA, Thyme SB, Li H, Ulge UY, Hovde BT, Baker D, Monnat RJ, Burt A, Crisanti A | display-authors = 6 | title = A synthetic homing endonuclease-based gene drive system in the human malaria mosquito | journal = Nature | volume = 473 | issue = 7346 | pages = 212–5 | date = May 2011 | pmid = 21508956 | pmc = 3093433 | doi = 10.1038/nature09937 | bibcode = 2011Natur.473..212W </ref> and fruit flies.<ref>>{{cite journal | vauthors = Chan YS, Naujoks DA, Huen DS, Russell S | title = Insect population control by homing endonuclease-based gene drive: an evaluation in Drosophila melanogaster | journal = Genetics | volume = 188 | issue = 1 | pages = 33–44 | date = May 2011 | pmid = 21368273 | pmc = 3120159 | doi = 10.1534/genetics.111.127506 </ref><ref>>{{cite journal | vauthors = Chan YS, Huen DS, Glauert R, Whiteway E, Russell S | title = Optimising homing endonuclease gene drive performance in a semi-refractory species: the Drosophila melanogaster experience | journal = PLOS ONE | volume = 8 | issue = 1 | pages = e54130 | date = 2013 | pmid = 23349805 | pmc = 3548849 | doi = 10.1371/journal.pone.0054130 | bibcode = 2013PLoSO...854130C </ref> However, homing endonucleases are sequence-specific. Altering their specificity to target other sequences of interest remains a major challenge.<ref> name=":1" </ref> The possible applications of gene drive remained limited until the discovery of CRISPR and associated RNA-guided endonucleases such as [[Cas9]] and [[CRISPR/Cpf1|Cpf1]].
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| − | In June 2014, the [[World Health Organization]] (WHO) Special Programme for Research and Training in Tropical Diseases<ref>>|url=https://www.who.int/tdr/about/en/|title=TDR | About us|date=|publisher=Who.int|access-date=2014-07-18</ref> issued guidelines<ref>>|url=https://www.who.int/tdr/news/2014/framwk-eval-gm-mosquitoes/en|title=TDR | A new framework for evaluating genetically modified mosquitoes|date=2014-06-26|publisher=Who.int|access-date=2014-07-18</ref> for evaluating genetically modified mosquitoes. In 2013 the [[European Food Safety Authority]] issued a protocol<ref>>{{cite journal|year=2013|title=EFSA - Guidance of the GMO Panel: Guidance Document on the ERA of GM animals|url=http://www.efsa.europa.eu/en/efsajournal/pub/3200|journal=EFSA Journal|volume=11|issue=5|pages=3200|doi=10.2903/j.efsa.2013.3200|access-date=2014-07-18|doi-access=free</ref> for [[environmental assessment]]s of all [[genetically modified organisms]].
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| − | === Funding ===
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| − | [[Target Malaria]], a project funded by the [[Bill & Melinda Gates Foundation|Bill and Melinda Gates Foundation]], invested $75 million in gene drive technology. The foundation originally estimated the technology to be ready for field use by 2029 somewhere in Africa. However, in 2016 Gates changed this estimate to some time within the following two years.<ref>>|url=https://www.technologyreview.com/s/602304/bill-gates-doubles-his-bet-on-wiping-out-mosquitoes-with-gene-editing/|title=Bill Gates doubles his bet on wiping out mosquitoes with gene editing|last=Regalado|first=Antonio| name-list-style = vanc |access-date=2016-09-20</ref> In December 2017, documents released under the [[Freedom of Information Act (United States)|Freedom of Information Act]] showed that [[DARPA]] had invested $100 million in gene drive research.<ref>>{{Cite news|url=https://www.theguardian.com/science/2017/dec/04/us-military-agency-invests-100m-in-genetic-extinction-technologies|title=US military agency invests $100m in genetic extinction technologies|last=Neslen|first=Arthur| name-list-style = vanc |date=2017-12-04|work=The Guardian|access-date=2017-12-04|language=en-GB|issn=0261-3077</ref>
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| − | == Control strategies ==
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| − | Scientists have designed multiple strategies to maintain control over gene drives.
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| − | The drosophila drive requires at least thousands of insects for the drive to begin. A few individuals escaping the target region would be unlikely to spread the drive.<ref>https://www.technologyreview.com/s/603533/first-gene-drive-in-mammals-could-aid-vast-new-zealand-eradication-plan/|title=First Gene Drive in Mammals Could Aid Vast New Zealand Eradication Plan|last=Regalado|first=Antonio| name-list-style = vanc |date=10 February 2017|location=MIT Tech Review|access-date=14 February 2017</ref>
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| − | In 2020 researchers reported the development of two active [[guide RNA]]-only elements that, according to their study, may enable halting or deleting gene drives introduced into populations in the wild with [[CRISPR-Cas9 gene editing]]. The paper's senior author cautions that the two neutralizing systems they demonstrated in cage trials "should not be used with a [[Security#Perceptions of security|false sense of security]] for field-implemented gene drives".<ref>>{{cite news |title=Biologists create new genetic systems to neutralize gene drives |url=https://phys.org/news/2020-09-biologists-genetic-neutralize-gene.html |accessdate=8 October 2020 |work=phys.org |language=en</ref><ref>>{{cite journal |last1=Xu |first1=Xiang-Ru Shannon |last2=Bulger |first2=Emily A. |last3=Gantz |first3=Valentino M. |last4=Klanseck |first4=Carissa |last5=Heimler |first5=Stephanie R. |last6=Auradkar |first6=Ankush |last7=Bennett |first7=Jared B. |last8=Miller |first8=Lauren Ashley |last9=Leahy |first9=Sarah |last10=Juste |first10=Sara Sanz |last11=Buchman |first11=Anna |last12=Akbari |first12=Omar S. |last13=Marshall |first13=John M. |last14=Bier |first14=Ethan |title=Active Genetic Neutralizing Elements for Halting or Deleting Gene Drives |journal=Molecular Cell |date=18 September 2020 |volume=80 |issue=2 |pages=246–262.e4 |doi=10.1016/j.molcel.2020.09.003 |pmid=32949493 |url=https://www.sciencedirect.com/science/article/abs/pii/S1097276520306110 |accessdate=8 October 2020 |language=en |issn=1097-2765</ref>
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| − | == CRISPR ==
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| − | [[CRISPR]]<ref>>{{cite journal|url=http://www.sciencemag.org/content/341/6148/833.summary?sid=03aa8081-376c-4e47-9efe-e453db28b20c|title=The CRISPR Craze|date=2013-08-23|publisher=Sciencemag.org| first = Elizabeth | last = Pennisi |journal=Science|volume=341|issue=6148|pages=833–6|doi=10.1126/science.341.6148.833|pmid=23970676|bibcode=2013Sci...341..833P| name-list-style = vanc |access-date=2014-07-18</ref> is a DNA editing method that makes genetic engineering faster, easier, and more efficient.<ref> name="NYT-20150511">{{cite news|url=https://www.nytimes.com/2015/05/12/science/jennifer-doudna-crispr-cas9-genetic-engineering.html|title=Jennifer Doudna, a Pioneer Who Helped Simplify Genome Editing|last=Pollack|first=Andrew| name-list-style = vanc |date=May 11, 2015|work=[[New York Times]]|access-date=May 12, 2015</ref> The approach involves expressing an [[RNA]]-guided [[endonuclease]] such as Cas9 along with guide RNAs directing it to a particular sequence to be edited. When the endonuclease cuts the target sequence, the cell repairs the damage by replacing the original sequence with homologous DNA. By introducing an additional template with appropriate homologues, an endonuclease can be used to delete, add or modify genes in an unprecedentedly simple manner. {{As of|2014, it had been tested in cells of 20 species, including humans.<ref> name="el14072"</ref> In many of these species, the edits modified the organism's [[germline]], allowing them to be inherited.
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| − | In 2014 Esvelt and coworkers first suggested that CRISPR/Cas9 might be used to build endonuclease gene drives.<ref> name="el14072"</ref> In 2015 researchers published successful engineering of CRISPR-based gene drives in ''[[Saccharomyces cerevisiae#Model organism|Saccharomyces]]''<ref> name=":3">{{cite biorxiv| vauthors = DiCarlo JE, Chavez A, Dietz SL, Esvelt KM, Church GM |year=2015|title=RNA-guided gene drives can efficiently and reversibly bias inheritance in wild yeast|biorxiv=10.1101/013896 </ref>'','' ''[[Drosophila#Laboratory-cultured animals|Drosophila]]'',<ref>>{{cite journal | vauthors = Gantz VM, Bier E | title = Genome editing. The mutagenic chain reaction: a method for converting heterozygous to homozygous mutations | journal = Science | volume = 348 | issue = 6233 | pages = 442–4 | date = April 2015 | pmid = 25908821 | pmc = 4687737 | doi = 10.1126/science.aaa5945 </ref> and [[mosquito]]es.<ref>>{{cite journal | vauthors = Gantz VM, Jasinskiene N, Tatarenkova O, Fazekas A, Macias VM, Bier E, James AA | title = Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 49 | pages = E6736-43 | date = December 2015 | pmid = 26598698 | pmc = 4679060 | doi = 10.1073/pnas.1521077112 | bibcode = 2015PNAS..112E6736G </ref><ref> name=":0">{{cite journal | vauthors = Hammond A, Galizi R, Kyrou K, Simoni A, Siniscalchi C, Katsanos D, Gribble M, Baker D, Marois E, Russell S, Burt A, Windbichler N, Crisanti A, Nolan T | display-authors = 6 | title = A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae | journal = Nature Biotechnology | volume = 34 | issue = 1 | pages = 78–83 | date = January 2016 | pmid = 26641531 | pmc = 4913862 | doi = 10.1038/nbt.3439 </ref> All four studies demonstrated efficient inheritance distortion over successive generations, with one study demonstrating the spread of a gene drive into laboratory populations.<ref> name=":0" </ref> Drive-resistant alleles were expected to arise for each of the described gene drives, however this could be delayed or prevented by targeting highly conserved sites at which resistance is expected to have a severe fitness cost.
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| − | Because of CRISPR's targeting flexibility, gene drives could theoretically be used to engineer almost any trait. Unlike previous designs, they could be tailored to block the evolution of drive resistance in the target population by targeting multiple sequences within appropriate genes. CRISPR could permit a variety of gene drive architectures intended to control rather than crash populations.
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| − | == Applications ==
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| − | Gene drives have two main classes of application, which have implications of different significance:
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| − | * introduce a genetic modification in laboratory populations; once a strain or a line carrying the gene drive has been produced, the drive can be passed to any other line by mating. Here the gene drive is used to achieve much more easily a task that could be accomplished with other techniques.
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| − | * introduce a genetic modification in wild populations. Gene drives constitute a major development that makes possible previously unattainable changes.
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| − | Because of their unprecedented potential risk, safeguard mechanisms have been proposed and tested.<ref> name=":3" </ref><ref>>{{cite journal | vauthors = DiCarlo JE, Chavez A, Dietz SL, Esvelt KM, Church GM | title = Safeguarding CRISPR-Cas9 gene drives in yeast | journal = Nature Biotechnology | volume = 33 | issue = 12 | pages = 1250–1255 | date = December 2015 | pmid = 26571100 | pmc = 4675690 | doi = 10.1038/nbt.3412 </ref>
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| − | === Disease vector species ===
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| − | One possible application is to genetically modify [[mosquito]]es and other disease vectors so that they cannot transmit diseases such as [[malaria]] and [[dengue fever]]. Researchers have claimed that by applying the technique to 1% of the wild population of mosquitoes, that they could eradicate malaria within a year.<ref>>{{Cite video|url=https://www.youtube.com/watch?v=OI_OhvOumT0|title=Gene editing can now change an entire species -- forever|date=2016-06-02|last=Kahn|first=Jennifer | name-list-style = vanc |language=en|publisher=TED</ref>
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| − | === Invasive species control ===
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| − | A gene drive could be used to eliminate [[invasive species]] and has, for example, been proposed as a way to eliminate [[invasive species in New Zealand]].<ref> name="NZ gene drive James Kalmakoff"> | url=http://www.merlinnz.com/blog/crispr-pest-free-nz/ | title=CRISPR for pest-free NZ | date=11 October 2016 | access-date=19 October 2016 | last = Kalmakoff | first = James | name-list-style = vanc </ref> Gene drives for biodiversity conservation purposes are being explored as part of The Genetic Biocontrol of Invasive Rodents (GBIRd) program because they offer the potential for reduced risk to non-target species and reduced costs when compared to traditional invasive species removal techniques. Given the risks of such an approach described below, the GBIRd partnership is committed to a deliberate, step-wise process that will only proceed with public alignment, as recommended by the world's leading gene drive researchers from the Australian and US National Academy of
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| − | Sciences and many others.<ref>> | url=http://www.geneticbiocontrol.org/wp-content/uploads/2018/05/GBIRD-FactSheet-April-2018.pdf | title=GBIRd Fact Sheet | date=1 April 2018 | access-date=14 November 2018 </ref> A wider Outreach Network for Gene Drive Research exists to raise awareness of the value of gene drive research for the public good.<ref>> | url=https://genedrivenetwork.org/resources/6-mission-principles-statement-july2018/file | title=Mission & Principles Statement | date=1 July 2018 | access-date=14 November 2018 </ref>
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| − | Some scientists are concerned about the technique, fearing it could spread and wipe out species in native habitats.<ref>> | url = http://theconversation.com/gene-drives-could-wipe-out-whole-populations-of-pests-in-one-fell-swoop-81681 | title = 'Gene drives' could wipe out whole populations of pests in one fell swoop | work = THE CONVERSATION </ref> The gene could mutate, potentially causing unforeseen problems (as could any gene).<ref>> | url = http://blogs.plos.org/dnascience/2017/11/30/an-argument-against-gene-drives-to-extinguish-new-zealand-mammals-life-finds-a-way/ | title = An Argument Against Gene Drives to Extinguish New Zealand Mammals: Life Finds a Way | work = Plos blogs </ref> Many non-native species can hybridize with native species, such that a gene drive afflicting a non-native plant or animal that hybridizes with a native species could doom the native species. Many non-native species have naturalized into their new environment so well that crops and/or native species have adapted to depend on them.<ref> name="NZ gene drive risks"> | url=https://www.odt.co.nz/opinion/risks-may-accompany-gene-drive-technology#comment-1086 | title=Risks may accompany gene drive technology | publisher=Otago Daily Times | date=17 October 2016 | access-date=19 October 2016 | last = Campbell | first = Colin | name-list-style = vanc </ref>
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| − | ==== Predator Free 2050 ====
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| − | {{main|Predator Free 2050
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| − | The Predator Free 2050 project is a New Zealand government program to completely eliminate eight invasive mammalian predator species (including rats, short-tailed weasels, and possums) from the country by 2050.<ref>>{{cite news|last1=Stockton|first1=Nick| name-list-style = vanc |title=How New Zealand Plans to Kill Its (Non-Human) Invasive Mammals|url=https://www.wired.com/2016/07/new-zealand-plans-kill-non-human-invasive-mammals/|work=WIRED|date=July 27, 2016</ref><ref> name="Scoop">|url=http://www.scoop.co.nz/stories/SC1701/S00024/predator-free-nz-expert-qa.htm|title=Predator Free NZ - Expert Q&A|date=17 January 2017|location=Scoop|access-date=17 January 2017</ref> The projects was first announced in 2016 by New Zealand's prime minister [[John Key]] and in January 2017 it was announced that gene drives would be used in the effort.<ref> name="Scoop" </ref> In 2017 one group in Australia and another in Texas released preliminary research into creating 'daughterless mice', using gene drives in mammals.<ref> name=":5" </ref>
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| − | ==== California ====
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| − | In 2017 scientists at the University of California, Riverside developed a gene drive to attack the [[Invasive species|invasive]] [[Drosophila suzukii|spotted-wing drosophila]], a type of fruit fly native to Asia that is costing California's cherry farms $700 million per year because of its tail's razor-edged “[[ovipositor]]” that destroys unblemished fruit. The primary alternative control strategy involves the use of [[insecticide]]s called [[pyrethroid]]s that kills almost all insects that it contacts.<ref> name=":4" </ref>
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| − | === Wild animal welfare ===
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| − | The transhumanist philosopher [[David Pearce (philosopher)|David Pearce]] has advocated for using CRISPR-based gene drives to reduce the [[suffering of wild animals]].<ref>>{{Cite journal|last=Vinding|first=Magnus| name-list-style = vanc |date=2018-08-01|title=Reducing Extreme Suffering for Non-Human Animals: Enhancement vs. Smaller Future Populations?|url=https://digitalcommons.calpoly.edu/bts/vol23/iss1/8|journal=Between the Species|volume=23|issue=1</ref> [[Kevin M. Esvelt]], an American biologist who has helped develop gene drive technology, has argued that there is a moral case for the elimination of the [[New World screwworm]] through such technologies because of the immense suffering that infested wild animals experience when they are eaten alive.<ref>>|title=When Are We Obligated To Edit Wild Creatures?|url=https://leapsmag.com/when-are-we-obligated-to-edit-wild-creatures/|last=Esvelt|first=Kevin| name-list-style = vanc |date=2019-08-30|website=leapsmag|language=en-US|access-date=2020-05-03</ref>
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| − | == External links ==
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| − | * [https://genedrivenetwork.org The Outreach Network for Gene Drive Research website]
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| − | * [http://www.geneticbiocontrol.org/ The Genetic Biocontrol of Invasive Rodents (GBIRd) program website]
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| − | * |title=Gene Drive from Harvard's Wyss Institute |publisher=Wyss Institute |date=2014-07-17 |access-date=2014-08-11|url=https://www.youtube.com/watch?v=Cy69C6vnFCQ/
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| − | [[Category:Genetic engineering]]
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| − | [[Category:Sterilization (medicine)]]
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| − | {{SMWDocs}}
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| − | ==References==
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| − | <references/>
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| − | {{PageCredit
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| − | |site=Wikipedia
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| − | |date=31 December 2020
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| − | |url=https://en.wikipedia.org/wiki/Gene_drive
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| − | }}
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