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

Germline Cas9 promoters with improved performance for homing gene drive DOI Creative Commons
Jie Du, Weizhe Chen,

Xihua Jia

et al.

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

Published: May 29, 2024

Abstract Gene drive systems could be a viable strategy to prevent pathogen transmission or suppress vector populations by propagating alleles with super-Mendelian inheritance. CRISPR-based homing gene drives convert wild type into in heterozygotes Cas9 and gRNA. It is thus desirable identify promoters that yield high conversion rates, minimize the formation rate of resistance both germline early embryo, limit somatic expression. In Drosophila , nanos promoter avoids leaky expression, but at cost embryo from maternally deposited Cas9. To improve efficiency, we test eleven melanogaster promoters. Some achieve higher efficiency minimal resistance, none completely avoid However, such expression often does not carry detectable fitness costs for rescue targeting haplolethal gene, suggesting conversion. Supporting 4-gRNA suppression drive, one leads low equilibrium frequency due other outperforms resulting successful cage population. Overall, these hold advantages species may possess valuable homologs organisms.

Language: Английский

Citations

10
Assessment of drive efficiency and resistance allele formation of a homing gene drive in the mosquito Aedes aegypti DOI

Xiaozhen Yang,

Xuejiao Xu,

Yixian Chen

et al.

Journal of Pest Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Language: Английский

Citations

1
Adversarial interspecies relationships facilitate population suppression by gene drive in spatially explicit models DOI
Yiran Liu, WeiJian Teo, Haochen Yang

et al.

Ecology Letters, Journal Year: 2023, Volume and Issue: 26(7), P. 1174 - 1185

Published: May 10, 2023

Suppression gene drives bias their inheritance to spread through a population, potentially eliminating it when they reach high frequency. CRISPR homing suppression have already seen success in the laboratory, but several models predict that may be elusive population with realistic spatial structure due extinction-recolonization cycles. Here, we extend our continuous space framework include two competing species or predator-prey pairs. We find both general and mosquito-specific models, predators can facilitate drive-based suppression, albeit at cost of an increased rate drive loss outcomes. These results are robust mosquito seasonal fluctuations. Our study illustrates difficulty predicting outcomes complex ecosystems. However, promising for prospects less powerful successfully eliminate target other pest populations.

Language: Английский

Citations

16
Population suppression by release of insects carrying a dominant sterile homing gene drive targeting doublesex in Drosophila DOI Creative Commons
Weizhe Chen,

Jialiang Guo,

Yiran Liu

et al.

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

Published: Sept. 14, 2024

Language: Английский

Citations

7
The potential of gene drives in malaria vector species to control malaria in African environments DOI Creative Commons
Penelope A. Hancock, Ace North, Adrian W. Leach

et al.

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

Published: Oct. 17, 2024

Gene drives are a promising means of malaria control with the potential to cause sustained reductions in transmission. In real environments, however, their impacts will depend on local ecological and epidemiological factors. We develop data-driven model investigate gene that causes vector population suppression. simulate drive releases sixteen ~ 12,000 km

Language: Английский

Citations

6
Experimental demonstration of tethered gene drive systems for confined population modification or suppression DOI Creative Commons
Matthew Metzloff, Emily Yang, Sumit Dhole

et al.

BMC Biology, Journal Year: 2022, Volume and Issue: 20(1)

Published: May 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.

Language: Английский

Citations

26
Anopheles homing suppression drive candidates exhibit unexpected performance differences in simulations with spatial structure DOI Creative Commons
Samuel E. Champer, Isabel K. Kim, Andrew G. Clark

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Oct. 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.

Language: Английский

Citations

25
The Challenges in Developing Efficient and Robust Synthetic Homing Endonuclease Gene Drives DOI Creative Commons
Sebald A. N. Verkuijl, Joshua X. D. Ang, Luke Alphey

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2022, Volume and Issue: 10

Published: March 28, 2022

Making discrete and precise genetic changes to wild populations has been proposed as a means of addressing some the world’s most pressing ecological public health challenges caused by insect pests. Technologies that would allow this, such synthetic gene drives, have under development for many decades. Recently, new generation programmable nucleases dramatically accelerated technological development. CRISPR-Cas9 improved efficiency engineering used principal effector nuclease in different drive inheritance biasing mechanisms. Of these nuclease-based homing endonuclease drives subject bulk research efforts (particularly insects), with iterations having developed upon similar core designs. We chart history development, highlighting emergence unintended repair outcomes, “leaky” expression, parental deposition. conclude discussing progress made developing strategies increase mitigate or prevent outcomes.

Language: Английский

Citations

19
Assessment of distant-site rescue elements for CRISPR toxin-antidote gene drives DOI Creative Commons

Jingheng Chen,

Xuejiao Xu, Jackson Champer

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2023, Volume and Issue: 11

Published: Feb. 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.

Language: Английский

Citations

11
Manipulating the Destiny of Wild Populations Using CRISPR DOI Creative Commons
Robyn Raban, John M. Marshall, Bruce A. Hay

et al.

Annual Review of Genetics, Journal Year: 2023, Volume and Issue: 57(1), P. 361 - 390

Published: Sept. 19, 2023

Genetic biocontrol aims to suppress or modify populations of species protect public health, agriculture, and biodiversity. Advancements in genome engineering technologies have fueled a surge research this field, with one gene editing technology, CRISPR, leading the charge. This review focuses on current state CRISPR for genetic pests highlights progress ongoing challenges using these approaches.

Language: Английский

Citations

11