Suppressing mosquito populations with precision guided sterile males

Li, Ming; Yang, Ting; Bui, Michelle; Gamez, Stephanie; Wise, Tyler; Kandul, Nikolay P.; Liu, Junru; Alcantara, Lenissa; Lee, Haena; Edula, Jyotheeswara R.; Raban, Robyn; Zhan, Yinpeng; Wang, Yijin; DeBeaubien, Nicolas A.; Chen, Jieyan; C., Héctor M. Sánchez; Bennett, Jared B.; Antoshechkin, Igor; Montell, Craig; Marshall, John M.; Akbari, Omar S.

doi:10.1038/s41467-021-25421-w

Cited by 81 publications

(99 citation statements)

References 36 publications

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“…Given the efficiency of Lethal Biallelic Mosaicism (LBM) 2 , 3 , 18 , 26 , we hypothesized that this mechanism could be exploited, in combination with sex chromosome-linked Cas9 elements, as a novel method for sex selection that we term SE x L ink E d C RISPR selec T ion (SELECT). To explore this hypothesis, we opted to target an essential haplosufficient gene, DNA Polymerase gamma subunit 2 ( PolG2 , DNA polymerase γ 35 kDa, CG33650) required for the replication and repair of mitochondrial DNA 34 .…”

Section: Resultsmentioning

confidence: 99%

“…5 ). We performed simulations for Anopheles gambiae , a mosquito disease vector that proof-of-concept gene-editing tools from D. melanogaster are often applied to 2 , 3 . Two populations with an equilibrium size of 10,000 were simulated, exchanging migrants at a rate of 1% per mosquito per generation 36 .…”

Section: Resultsmentioning

confidence: 99%

“…The capacity to encode CRISPR-based gene-editing components within insect genomes, coupled with the ability to precisely orchestrate endogenous activity in every individual containing them, has inspired the exploration of novel methods that can modify insects in the population level 1 . For example, CRISPR-mediated genetic engineering can be used for large-scale manipulation of laboratory-reared individuals to produce phenotypes useful for genetic sexing, or male (♂) sterility, prior to release 2 , 3 . CRISPR-mediated modifications can also be used in sustainable suppression strategies aimed at reducing or eliminating wild populations, or in modification strategies directed to increasing the frequency of a desired allele or genotype, such as pathogen resistance, within a population.…”

Section: Introductionmentioning

confidence: 99%

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Exploiting a Y chromosome-linked Cas9 for sex selection and gene drive

et al. 2021

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CRISPR-based genetic engineering tools aimed to bias sex ratios, or drive effector genes into animal populations, often integrate the transgenes into autosomal chromosomes. However, in species with heterogametic sex chromsomes (e.g. XY, ZW), sex linkage of endonucleases could be beneficial to drive the expression in a sex-specific manner to produce genetic sexing systems, sex ratio distorters, or even sex-specific gene drives, for example. To explore this possibility, here we develop a transgenic line of Drosophila melanogaster expressing Cas9 from the Y chromosome. We functionally characterize the utility of this strain for both sex selection and gene drive finding it to be quite effective. To explore its utility for population control, we built mathematical models illustrating its dynamics as compared to other state-of-the-art systems designed for both population modification and suppression. Taken together, our results contribute to the development of current CRISPR genetic control tools and demonstrate the utility of using sex-linked Cas9 strains for genetic control of animals.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exploiting a Y chromosome-linked Cas9 for sex selection and gene drive

et al. 2021

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“…Release of insects with dominant lethality (RIDL), has been successfully demonstrated to suppress target mosquito populations in field trials in the Caribbean islands and South America ( Harris et al, 2012 ). Precision-guided SIT (pgSIT) utilizes expression of Cas9 nuclease to knock out female survival and male fertility genes prior to generate potential biocontrol agents ( Li et al, 2021 ; Kandul et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Genetically engineered insects with sex-selection and genetic incompatibility enable population suppression

Upadhyay

Feltman

Sychla

et al. 2022

eLife

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Engineered Genetic Incompatibility (EGI) is a method to create species-like barriers to sexual reproduction. It has applications in pest control that mimic Sterile Insect Technique when only EGI males are released. This can be facilitated by introducing conditional female-lethality to EGI strains to generate a sex-sorting incompatible male system (SSIMS). Here, we demonstrate a proof of concept by combining tetracycline-controlled female lethality constructs with a pyramus-targeting EGI line in the model insect Drosophila melanogaster. We show that both functions (incompatibility and sex-sorting) are robustly maintained in the SSIMS line and that this approach is effective for population suppression in cage experiments. Further we show that SSIMS males remain competitive with wild-type males for reproduction with wild-type females, including at the level of sperm competition.

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“…Other promising technologies, including precision-guided sterile insect technique (pgSIT) have been developed for the purposes of localized, confinable management of Ae. aegypti populations (Li et al, 2020;Li et al, 2021). Another genetic control strategy, termed population replacement, aims at spreading an antipathogen (i.e., antiviral) effector through a targeted mosquito population.…”

Section: Introductionmentioning

confidence: 99%

Assessing single-component gene drive systems in the mosquito Aedes aegypti via single generation crosses and modeling

Reid

Lin

Williams

et al. 2021

Preprint

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The yellow fever mosquito Aedes aegypti is a major vector of arthropod-borne viruses, including dengue, chikungunya, and Zika. A novel approach to mitigate arboviral infections is to generate mosquitoes refractory to infection by overexpressing antiviral effector molecules. Such an approach requires a mechanism to spread these antiviral effectors through a population, for example, by using CRISPR/Cas9-based gene drive systems. Here we report an autonomous single-component gene drive system in Ae. aegypti that is designed for persistent population replacement. Critical to the design of a single-locus autonomous gene drive is that the selected genomic locus be amenable to both gene drive and the appropriate expression of the antiviral effector. In our study, we took a reverse engineering approach to target two genomic loci ideal for the expression of antiviral effectors and further investigated the use of three promoters for Cas9 expression (nanos, β2-tubulin, or zpg) for the gene drive. We found that both promoter selection and genomic target site strongly influenced the efficiency of the drive, resulting in 100% inheritance in some crosses. We also observed the formation of inheritable gene drive blocking indels (GDBI) in the genomic locus with the highest levels of gene drive. Overall, our drive system forms a platform for the further testing of driving antipathogen effector genes through Ae. aegypti populations.

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Suppressing mosquito populations with precision guided sterile males

Cited by 81 publications

References 36 publications

Exploiting a Y chromosome-linked Cas9 for sex selection and gene drive

Exploiting a Y chromosome-linked Cas9 for sex selection and gene drive

Genetically engineered insects with sex-selection and genetic incompatibility enable population suppression

Assessing single-component gene drive systems in the mosquito Aedes aegypti via single generation crosses and modeling

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