Deployment of tethered gene drive for confined suppression in continuous space requires avoiding drive wave interference DOI

Ruobing Feng,

Jackson Champer

Molecular Ecology, Journal Year: 2024, Volume and Issue: 33(19)

Published: Sept. 16, 2024

Abstract Gene drives have great potential for suppression of pest populations and removal exotic invasive species. CRISPR homing drive is a powerful but unconfined drive, posing risks uncontrolled spread. Thus, developing methods confining gene significance. Tethered combines confined system such as Toxin‐Antidote Recessive Embryo with strong drive. It can prevent the from spreading beyond be constructed readily, giving it good prospects future development. However, we found that care must taken when deploying tethered systems in some scenarios. Simulations panmictic population model reveal successful deployment requires proper release ratio between two components, tailored to eliminating before has chance Spatial models where moves over one‐dimensional landscape display more serious phenomenon wave interference components. If faster catches up wave, success still possible, dependent on performance ecological parameters. Two‐dimensional simulations further restrict parameter range success. careful consideration given conditions, well specific proposals application systems.

Language: Английский

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
Performance characteristics allow for confinement of a CRISPR toxin–antidote gene drive for population suppression in a reaction–diffusion model DOI
Shijie Zhang, Jackson Champer

Proceedings of the Royal Society B Biological Sciences, Journal Year: 2024, Volume and Issue: 291(2025)

Published: June 1, 2024

Gene drive alleles that can bias their own inheritance could engineer populations for control of disease vectors, invasive species and agricultural pests. There are successful examples suppression drives confined modification drives, but developing has proven more difficult. However, CRISPR-based toxin–antidote dominant embryo (TADE) may fill this niche. It works by targeting disrupting a haplolethal target gene in the germline with its gRNAs while rescuing target. also disrupts female fertility driving insertion or additional gRNAs. Here, we used reaction–diffusion model to assess performance continuous space, where outcomes be substantially different from those panmictic populations. We measured wave speed found moderate fitness costs disruption early maternally deposited nuclease eliminate drive’s ability form advance. assessed required release size, finally investigated migration corridor scenarios. is often possible suppress one population then persist without invading second population, potentially desirable outcome. Thus, even imperfect variants TADE excellent candidates suppression.

Language: Английский

Citations

3
Deployment of tethered gene drive for confined suppression in continuous space requires avoiding drive wave interference DOI

Ruobing Feng,

Jackson Champer

Molecular Ecology, Journal Year: 2024, Volume and Issue: 33(19)

Published: Sept. 16, 2024

Abstract Gene drives have great potential for suppression of pest populations and removal exotic invasive species. CRISPR homing drive is a powerful but unconfined drive, posing risks uncontrolled spread. Thus, developing methods confining gene significance. Tethered combines confined system such as Toxin‐Antidote Recessive Embryo with strong drive. It can prevent the from spreading beyond be constructed readily, giving it good prospects future development. However, we found that care must taken when deploying tethered systems in some scenarios. Simulations panmictic population model reveal successful deployment requires proper release ratio between two components, tailored to eliminating before has chance Spatial models where moves over one‐dimensional landscape display more serious phenomenon wave interference components. If faster catches up wave, success still possible, dependent on performance ecological parameters. Two‐dimensional simulations further restrict parameter range success. careful consideration given conditions, well specific proposals application systems.

Language: Английский

Citations

1