Engineering drive-selection balance for localised population suppression with neutral dynamics DOI Creative Commons
Katie Willis, Austin Burt

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 21, 2024

Abstract Whilst the release of sterile males has been highly successful in suppressing some pest populations, it is impractical for other 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 localised. One way achieve would have perfect balance, all construct frequencies, between drive increasing and selection decreasing it. Here we describe create balance involving toxin-antidote causes recessive lethality, encodes genomic editor makes dominant lethal edits genome, provides protection against action or consequences editing. Computer modelling shows design 100-fold than males, 1000-fold when released alongside booster. We designs CRISPR-based molecular construction, including options avoid using recoded genes as antidotes.

Language: Английский

A homing rescue gene drive with multiplexed gRNAs reaches high frequency in cage populations but generates functional resistance DOI
Shibo Hou,

Jingheng Chen,

Ruobing Feng

et al.

Journal of genetics and genomics/Journal of Genetics and Genomics, Journal Year: 2024, Volume and Issue: 51(8), P. 836 - 843

Published: April 8, 2024

Language: Английский

Citations

3
A Y chromosome-linked genome editor for efficient population suppression in the malaria vectorAnopheles gambiae DOI Creative Commons
Ignacio Tolosana, Katie Willis, Austin Burt

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 14, 2024

ABSTRACT Genetic control – the deliberate introduction of genetic traits to a pest or vector population offers powerful tool augment conventional mosquito tools that have been successful in reducing malaria burden but are compromised by range operational challenges. Self-sustaining strategies shown great potential laboratory settings hesitancy due their invasive and persistent nature may delay implementation. Here instead we describe self-limiting strategy, designed geographically and/or temporally restricted effect, based on Y chromosome-linked genome editor (YLE). The YLE comprises CRISPR-Cas9 construct is always inherited males yet generates an autosomal dominant mutation transmitted over 90% offspring results female-specific sterility. Males unaffected. To our knowledge, system represents first engineering chromosome generate strain for mosquitoes. Mathematical modelling shows this technology up 8 times more efficient suppression than optimal versions other strategies.

Language: Английский

Citations

3
Improving the suppressive power of homing gene drive by co-targeting a distant-site female fertility gene DOI Creative Commons
Nicky R. Faber, Xuejiao Xu,

Jingheng Chen

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 26, 2024

Gene drive technology has the potential to address major biological challenges. Well-studied homing suppression drives have been shown be highly efficient in Anopheles mosquitoes, but for other organisms, lower rates of conversion prevent elimination target population. To tackle this issue, we propose a gene design that two targets: site where takes place, and distant cleavage induces population suppression. We model find two-target system allows occur over much wider range efficiency. Specifically, cutting efficiency now determines suppressive power drive, rather than as standard drives. construct Drosophila melanogaster show both components function successfully. However, embryo from maternal deposition well fitness costs female heterozygotes remain significant challenges Overall, our improved ease problems associated with many species is less efficient.

Language: Английский

Citations

3
Doublesex is essential for masculinization but not feminization in Lygus hesperus DOI
J. Joe Hull, Chan C. Heu,

Roni J. Gross

et al.

Insect Biochemistry and Molecular Biology, Journal Year: 2024, Volume and Issue: 166, P. 104085 - 104085

Published: Feb. 2, 2024

Language: Английский

Citations

2
Engineering drive-selection balance for localised population suppression with neutral dynamics DOI Creative Commons
Katie Willis, Austin Burt

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 21, 2024

Abstract Whilst the release of sterile males has been highly successful in suppressing some pest populations, it is impractical for other 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 localised. One way achieve would have perfect balance, all construct frequencies, between drive increasing and selection decreasing it. Here we describe create balance involving toxin-antidote causes recessive lethality, encodes genomic editor makes dominant lethal edits genome, provides protection against action or consequences editing. Computer modelling shows design 100-fold than males, 1000-fold when released alongside booster. We designs CRISPR-based molecular construction, including options avoid using recoded genes as antidotes.

Language: Английский

Citations

2