Toward the Definition of Efficacy and Safety Criteria for Advancing Gene Drive-Modified Mosquitoes to Field Testing

James, Stephanie; Marshall, John M.; Christophides, George K.; Okumu, Fredros O.; Nolan, Tony

doi:10.1089/vbz.2019.2606

Cited by 72 publications

(108 citation statements)

References 60 publications

(54 reference statements)

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“…Overall, the laboratory assessments conducted so far, carried out in line with the recommended phased pathway for testing gene-drive mosquitoes [37][38][39] , show that the characteristics of the Reckh gene-drive are likely to conform with those defined as part of a proposed Target Product Profile for population modification of mosquito strains 30 once the addition of the anti-malaria effectors is proven effective under this configuration. The highly efficient performance of the Reckh drive system makes it an excellent candidate for genetic control of an important malaria mosquito, An.…”

Section: Discussionmentioning

confidence: 99%

Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi

et al. 2020

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Cas9/gRNA-mediated gene-drive systems have advanced development of genetic technologies for controlling vector-borne pathogen transmission. These technologies include population suppression approaches, genetic analogs of insecticidal techniques that reduce the number of insect vectors, and population modification (replacement/alteration) approaches, which interfere with competence to transmit pathogens. Here, we develop a recoded gene-drive rescue system for population modification of the malaria vector, Anopheles stephensi, that relieves the load in females caused by integration of the drive into the kynurenine hydroxylase gene by rescuing its function. Non-functional resistant alleles are eliminated via a dominantly-acting maternal effect combined with slower-acting standard negative selection, and rare functional resistant alleles do not prevent drive invasion. Small cage trials show that single releases of gene-drive males robustly result in efficient population modification with ≥95% of mosquitoes carrying the drive within 5-11 generations over a range of initial release ratios.

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Section: Discussionmentioning

confidence: 99%

Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi

et al. 2020

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“…However, work on development and delivery objectives is needed to define final products and performance. Target product profiles (TPP) have been drafted and provide the basis for evaluating products for field use ( 5 , 6 ). TPPs comprise a list of key parameters, including drive efficiency, effector efficacy, genetic load (fitness), safety, production needs and release strategies, and a description of the ideal and the minimally-essential requirements for the product to have a practical value.…”

mentioning

confidence: 99%

Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae

Carballar-Lejarazú

Ogaugwu

Tushar

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

185

216

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A Cas9/guide RNA-based gene drive strain, AgNosCd-1, was developed to deliver antiparasite effector molecules to the malaria vector mosquito, Anopheles gambiae. The drive system targets the cardinal gene ortholog producing a red-eye phenotype. Drive can achieve 98 to 100% in both sexes and full introduction was observed in small cage trials within 6 to 10 generations following a single release of gene-drive males. No genetic load resulting from the integrated transgenes impaired drive performance in the trials. Potential drive-resistant target-site alleles arise at a frequency <0.1, and five of the most prevalent polymorphisms in the guide RNA target site in collections of colonized and wild-derived African mosquitoes do not prevent cleavage in vitro by the Cas9/guide RNA complex. Only one predicted off-target site is cleavable in vitro, with negligible deletions observed in vivo. AgNosCd-1 meets key performance criteria of a target product profile and can be a valuable component of a field-ready strain for mosquito population modification to control malaria transmission.

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“…Overall, the laboratory assessments conducted on this novel system, carried out in line with the recommended phased pathway for testing gene-drive mosquitoes [37][38][39] , show that the characteristics of the Rec gene-drive conform with those defined as part of a proposed Target Product Profile for population modification of mosquito strains 30 . The highly efficient performance of the Rec drive system makes it an excellent candidate for genetic control of an important malaria mosquito, An.…”

Section: Discussionmentioning

confidence: 94%

Efficient population modification gene-drive rescue system in the malaria mosquitoAnopheles stephensi

Adolfi¹,

Jasinskiene²,

Lee³

et al. 2020

Preprint

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The development of Cas9/gRNA-mediated gene-drive systems has bolstered the advancement of genetic technologies for controlling vector-borne pathogen transmission. These include population suppression approaches, genetic analogs of insecticidal techniques that reduce the number of vector insects, and population modification (replacement/alteration) approaches, which interfere with competence to transmit pathogens. We developed a recoded gene-drive rescue system for population modification in the malaria vector, Anopheles stephensi, that relieves the load in females caused by integration of the drive into the kynurenine hydroxylase gene by rescuing its function. Non-functional resistant alleles are eliminated via a dominantly-acting maternal effect combined with slower-acting standard negative selection, and a functional resistant allele does not prevent drive invasion. Small cage trials show that single releases of gene-drive males robustly result in efficient population modification with >95% of mosquitoes carrying the drive within 5-11 generations over a range of initial release ratios.

show abstract

Toward the Definition of Efficacy and Safety Criteria for Advancing Gene Drive-Modified Mosquitoes to Field Testing

Cited by 72 publications

References 60 publications

Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi

Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi

Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae

Efficient population modification gene-drive rescue system in the malaria mosquitoAnopheles stephensi

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