Adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post‐market environmental monitoring of genetically modified insects containing engineered gene drives

EFSA Journal, Год журнала: 2020, Номер 18(11)

Опубликована: Ноя. 1, 2020

Advances in molecular and synthetic biology are enabling the engineering of gene drives insects for disease vector/pest control.Engineered (that bias their own inheritance) can be designed either to suppress interbreeding target populations or modify them with a new genotype.Depending on engineered drive system, theoretically, genetic modification interest could spread through persist indefinitely, restricted its persistence.While research applications is advancing at fast pace, it will take several years technological developments move practical deliberate release into environment.Some modified (GDMIs) have been tested experimentally laboratory, but none has assessed small-scale confined field trials open as yet.There concern that GDMIs environment may possible irreversible unintended consequences.As proactive measure, European Food Safety Authority (EFSA) requested by Commission review whether previously published guidelines risk assessment genetically animals (EFSA, 2012 2013), including (GMIs), adequate sufficient GDMIs, primarily vectors, agricultural pests invasive species, environment.Under this mandate, EFSA was not develop GDMIs.In Scientific Opinion, Panel Genetically Modified Organisms (GMO) concludes EFSA's adequate, insufficient characterisation (MC), environmental (ERA) post-market monitoring (PMEM) GDMIs.While MC, ERA PMEM build existing framework GMIs do contain drives, there specific areas where further guidance needed GDMIs.

Язык: Английский

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Split versions of Cleave and Rescue selfish genetic elements for measured self limiting gene drive

PLoS Genetics, Год журнала: 2021, Номер 17(2), С. e1009385 - e1009385

Опубликована: Фев. 18, 2021

Gene drive elements promote the spread of linked traits, providing methods for changing composition or fate wild populations. Drive mechanisms that are self-limiting attractive because they allow control over duration and extent trait in time space, reversible through natural selection as wanes. Self-sustaining Cleave Rescue ( ClvR ) include a DNA sequence-modifying enzyme such Cas9/gRNAs disrupts endogenous versions an essential gene, tightly recoded version gene resistant to cleavage (the ), Cargo. spreads by creating loss-of-function (LOF) conditions which those without die lack functional copies gene. We use modeling show when -Cargo one both components required LOF allele creation (Cas9 gRNA) reside at different locations (split is due progressive decrease Cas9 frequency, thus opportunities alleles, occurs. Importantly, strength can be extended measured manner—which still self-limiting—by moving two close enough each other experience some degree linkage. With linkage, transiently experiences hitchhiking with until linkage disequilibrium between disappears, function recombination frequency number generations, novel point control. implement split Drosophila , key on chromosomes. Cargo/ /gRNAs high Cas9-dependent manner, while decreases. These observations measured, transient drive, coupled loss future potential, achieved using simple toolkit make up elements—Cas9 gRNAs /Cargo.

Язык: Английский

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Modelling homing suppression gene drive in haplodiploid organisms

Proceedings of the Royal Society B Biological Sciences, Год журнала: 2022, Номер 289(1972)

Опубликована: Апрель 13, 2022

Gene drives have shown great promise for suppression of pest populations. These engineered alleles can function by a variety mechanisms, but the most common is CRISPR homing drive, which converts wild-type to drive in germline heterozygotes. Some potential target species are haplodiploid, males develop from unfertilized eggs and thus only one copy each chromosome. This prevents conversion, substantial disadvantage compared diploids where conversion take place both sexes. Here, we study gene haplodiploids find that targeting female fertility could still be successful. However, such less powerful than suffer more functional resistance alleles. They substantially vulnerable high allele formation embryo owing maternally deposited Cas9 guide RNA also somatic cleavage activity. Examining spatial models organisms move over continuous landscape, haplodiploid surprisingly perform nearly as well diploids, possibly their ability spread further before inducing strong suppression. Together, these results indicate potentially used effectively suppress

Язык: Английский

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Experimental demonstration of tethered gene drive systems for confined population modification or suppression

BMC Biology, Год журнала: 2022, Номер 20(1)

Опубликована: Май 24, 2022

Homing gene drives hold great promise for the genetic control of natural populations. However, current homing systems are capable spreading uncontrollably between populations connected by even marginal levels migration. This could represent a substantial sociopolitical barrier to testing or deployment such and may generally be undesirable when objective is only local population control, as suppression an invasive species outside its native range. Tethered drive systems, in which locally confined provides CRISPR nuclease needed drive, provide solution this problem, offering power confinement supporting drive.

Язык: Английский

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Anopheles homing suppression drive candidates exhibit unexpected performance differences in simulations with spatial structure

eLife, Год журнала: 2022, Номер 11

Опубликована: Окт. 14, 2022

Recent experiments have produced several Anopheles gambiae homing gene drives that disrupt female fertility genes, thereby eventually inducing population collapse. Such may be highly effective tools to combat malaria. One such drive, based on the zpg promoter driving CRISPR/Cas9, was able eliminate a cage of mosquitoes. A second version, purportedly improved upon first by incorporating an X-shredder element (which biases inheritance towards male offspring), similarly successful. Here, we analyze experimental data from each these extract their characteristics and performance parameters compare previous interpretations performance. We assess suppression drive within individual-based simulation framework models mosquito dynamics in continuous space. find combined homing/X-shredder is actually less at context our model. In particular, often fails completely suppress population, instead resulting unstable equilibrium between wild-type alleles. By contrast, otherwise similar nos prove more promising candidates for future development than originally thought.

Язык: Английский

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Knockout of the odorant receptor co-receptor, orco, impairs feeding, mating and egg-laying behavior in the fall armyworm Spodoptera frugiperda

Insect Biochemistry and Molecular Biology, Год журнала: 2022, Номер 152, С. 103889 - 103889

Опубликована: Дек. 7, 2022

Язык: Английский

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Double drives and private alleles for localised population genetic control

PLoS Genetics, Год журнала: 2021, Номер 17(3), С. e1009333 - e1009333

Опубликована: Март 23, 2021

Synthetic gene drive constructs could, in principle, provide the basis for highly efficient interventions to control disease vectors and other pest species. This efficiency derives part from leveraging natural processes of dispersal flow spread construct its impacts one population another. However, sometimes (for example, with invasive species) only specific populations are need control, on non-target would be undesirable. Many designs use nucleases that recognise cleave genomic sequences, way restrict their exploit sequence differences between target populations. In this paper we propose model a series low threshold double suppression, each consisting two constructs, imposing reproductive load inserted into differentiated locus controlling first. Simple deterministic, discrete-generation computer simulations used assess alternative designs. We find simplest significantly more robust pre-existing cleavage resistance at than single designs, complex incorporating sex ratio distortion can still, even allowing successful when is neutral there up 50% population. Similar also replacement, similar benefits. A analysis CRISPR PAM sites island mainland malaria mosquito Anopheles gambiae indicates differentiation needed our methods work exist nature. Double drives should considered but localised genetic some

Язык: Английский

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Assessment of distant-site rescue elements for CRISPR toxin-antidote gene drives

Frontiers in Bioengineering and Biotechnology, Год журнала: 2023, Номер 11

Опубликована: Фев. 13, 2023

Gene drive is a genetic engineering technology that can enable super-mendelian inheritance of specific alleles, allowing them to spread through population. New gene types have increased flexibility, offering options for confined modification or suppression target populations. Among the most promising are CRISPR toxin-antidote drives, which disrupt essential wild-type genes by targeting with Cas9/gRNA. This results in their removal, increasing frequency drive. All these drives rely on having an effective rescue element, consists recoded version gene. element be at same site as gene, maximizing chance efficient rescue, distant site, allows useful such easily disrupting another confinement. Previously, we developed homing haplolethal and haplosufficient These successful had functional elements but suboptimal efficiency. Here, attempted construct distant-site configuration from three loci Drosophila melanogaster . We found additional gRNAs cut rates nearly 100%. However, all failed both genes. Furthermore, one minimally sequence was used template homology-directed repair different chromosomal arm, resulting formation resistance alleles. Together, inform design future CRISPR-based drives.

Язык: Английский

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Engineering drive–selection balance for localized population suppression with neutral dynamics

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(6)

Опубликована: Фев. 4, 2025

While the release of sterile males has been highly successful in suppressing some pest populations, it is impractical for many species due to disappearing after a single generation, necessitating large, repeated releases maintain sufficient impact. Synthetic gene drives promise more efficient approaches since they can increase frequency from rare, yet this also allows them spread across landscape, which may not always be desired. Between these two extremes are selectively neutral genetic constructs persist at released, offering potential suppression that remains localized. One way achieve would have perfect balance, all construct frequencies, between drive increasing and selection decreasing it. Here, we describe closely approximate balance using toxin–antidote causes recessive lethality or sterility, encodes genomic editor makes dominant lethal edits genome, provides protection against action consequences editing. Computer modeling shows design 100-fold than males, 1,000-fold when released alongside booster. We designs CRISPR-based molecular construction, including options avoid recoded genes as antidotes.

Язык: Английский

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Genetic engineering for SIT application: a fruit fly‐focused review

Insect Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 7, 2025

Abstract Sterile insect technique (SIT) has become a key component of efficient pest control. Fruit fly pests from the Drosophilidae and Tephritidae families pose substantial overwhelmingly increasing threat to agricultural industry, aggravated by climate change globalization among other contributors. In this review, we discuss advances in genetic engineering aimed improve SIT‐mediated fruit This includes SIT enhancement strategies such as novel sexing strain female lethality approaches. Self‐pervasive X‐shredding X‐poisoning sex distorters, alongside gene drive varieties are also reviewed. The self‐limiting precision‐guided SIT, which aims tackle removal male fertility via CRISPR/Cas9, is additionally introduced. By using examples existing tools interest, well model species, illustrate that population control intensity may be modulated depending on strategy selection.

Язык: Английский

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