Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi.
Adriana Adolfi,Adriana Adolfi,Valentino M. Gantz,Nijole Jasinskiene,H. K. Lee,Kristy S. Hwang,Gerard Terradas,Emily A. Bulger,Arunachalam Ramaiah,Jared B. Bennett,J. J. Emerson,John M. Marshall,Ethan Bier,Anthony A. James +13 more
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TLDR
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 is developed.Abstract:
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.read more
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Harnessing Wolbachia cytoplasmic incompatibility alleles for confined gene drive: A modeling study
Jiahe Li,Jackson Champer +1 more
TL;DR: It is found that a drive containing CifA and CifB together create a confined drive with a moderate to high introduction threshold, and when introduced separately, they act as a self-limiting drive.
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Closing the gap to effective gene drive in Aedes aegypti by exploiting germline regulatory elements
Michelle A. E. Anderson,Estela Gonzalez,Joshua Xin De Ang,Lewis Shackleford,Katherine Nevard,Sebald Verkuijl,Matthew P. Edgington,Tim Harvey-Samuel,Luke Alphey +8 more
TL;DR: In this paper , the authors showed that sds3G1-Cas9 could enable the spread of the kmosgRNAs element to either reach a higher (by ~15 percentage point) maximum carrier frequency or to achieve similar maximum carrier frequencies faster (by 12 generations) when compared to two other established split drive systems.
Journal ArticleDOI
CopyCatchers are versatile active genetic elements that detect and quantify inter-homolog somatic gene conversion
Zhiqian Li,Nimi Marcel,Sushil Devkota,Ankush Auradkar,Stephen M. Hedrick,Valentino M. Gantz,Ethan Bier +6 more
TL;DR: In this paper, the authors developed CopyCatchers to detect and quantify somatic gene conversion (SGC) events in Drosophila eye and thoracic epidermis, which can serve as effective discovery platforms to inform potential gene therapy strategies.
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A homing suppression gene drive with multiplexed gRNAs maintains high drive conversion efficiency and avoids functional resistance alleles
Emily Yang,Metzloff M,Anna Maria Langmüller,Andrew G. Clark,Philipp W. Messer,Jackson Champer,Jackson Champer +6 more
TL;DR: In this article, the authors constructed a homing suppression drive in Drosophila melanogaster that utilized multiplexed gRNAs to inhibit the formation of functional resistance alleles in its female fertility target gene.
Posted ContentDOI
Fitness effects of CRISPR endonucleases in Drosophila melanogaster populations
Anna Maria Langmüller,Jackson Champer,Lapinska S,Lei Xie,Metzloff M,Jingxian Liu,Yineng Xu,Andrew G. Clark,Philipp W. Messer +8 more
TL;DR: In this article, the fitness effects of genomic CRISPR/Cas9 expression in Drosophila melanogaster cage populations were assessed by tracking allele frequencies of four different transgenic constructs, designed to disentangle direct fitness costs due to the integration, expression, and target-site activity of Cas9 from potential off-target cleavage.
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