Manipulating the Destiny of Wild Populations Using CRISPR

Raban, Robyn; Marshall, John M.; Hay, Bruce A.; Akbari, Omar S.

doi:10.1146/annurev-genet-031623-105059

Cited by 8 publications

(7 citation statements)

References 239 publications

(366 reference statements)

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“…Outcomes are comparable to those observed when ClvR is introduced at a frequency of 10%, and all elements are intact (Fig. 5d-f re generally detrimental to gene drive (reviewed in 1,3 ). Resistant versions of the essential gene can allow non-ClvR chromosomes to survive in gametes produced by ClvR carriers.…”

Section: Clvr Drive Behavior In Response To Mutations In Cis and Transsupporting

confidence: 56%

“…An alternative strategy for population suppression in some plants is suggested by modeling and experiments in animals focused on the creation of sex-linked gamete killers. The goal of these efforts is to create Y-linked killers of X-chromosome-bearing sperm, resulting in males that only produce male progeny (reviewed in 1,3 ). Such a system can be used to drive population suppression or elimination (towards an all-male state) when sperm is not limiting and females mate with one or a few males 13,42 .…”

Section: Discussionmentioning

confidence: 99%

“…Related to this last point, gene drive is easily detected if searched for, either through observation of phenotypic changes in a population or through genome sequencing. Finally, gene drive for population suppression can and has been blocked-many times-through the creation of resistant alleles (reviewed in 1,3 ). It has also been blocked through introduction of a transgene that inhibits Cas9 function 99,100 , and it can in principle be blocked using a second modification drive that actively targets key components of the initial drive element of concern.…”

Section: Discussionmentioning

confidence: 99%

“…The results of modeling and lab experiments demonstrate this can result in spread of these "cargo" genes to high frequency in an extant population. Alternatively, drive can result in population suppression or elimination if spread of the element drives the population towards an unfit set of genotypes (e.g., all male, all females sterile), reviewed in [1][2][3] .…”

Section: Mainmentioning

confidence: 99%

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Cleave and Rescue gamete killers create conditions for gene drive in plants

Oberhofer,

Johnson,

Ivy

et al. 2023

Preprint

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Gene drive elements promote the spread of linked traits, even when their presence confers a fitness cost to carriers, and can be used to change the composition or fate of wild populations. Cleave and Rescue (ClvR) drive elements sit at a fixed chromosomal position and include a DNA sequence-modifying enzyme such as Cas9/gRNAs (the Cleaver/Toxin) that disrupts endogenous versions of an essential gene, and a recoded version of the essential gene resistant to cleavage (the Rescue/Antidote).ClvRspreads by creating conditions in which those lackingClvRdie because they lack functional versions of the essential gene. We demonstrate the essential features ofClvRgene drive in the plantArabidopsis thalianathrough killing of gametes that fail to inherit aClvRthat targets the essential gene YKT61, whose expression is required in male and female gametes for their survival. Resistant (uncleavable but functional) alleles, which can slow or prevent drive, were not observed. Modeling shows plantClvRs can be used to rapidly drive population modification or suppression. Possible applications in weed control, plant breeding and conservation are discussed.

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Section: Clvr Drive Behavior In Response To Mutations In Cis and Transsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Mainmentioning

confidence: 99%

See 2 more Smart Citations

Cleave and Rescue gamete killers create conditions for gene drive in plants

Oberhofer,

Johnson,

Ivy

et al. 2023

Preprint

Self Cite

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“…Recent advancements in genome engineering technologies have facilitated the development of a variety of genetic approaches for controlling pest populations. These involve releasing modified members of the pest species designed to mate with those in the wild and reduce harm (Grilli et al, 2021, Raban et al, 2023). One approach is for the released individuals to suppress the density of the population by interfering with its ability to successfully reproduce, thereby reducing the overall harm caused.…”

Section: Introductionmentioning

confidence: 99%

Engineering drive-selection balance for localised population suppression with neutral dynamics

Willis,

Burt

2024

Preprint

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Whilst the release of sterile males has been highly successful in suppressing some pest populations, it is impractical for other species due to the males disappearing after a single generation, necessitating large, repeated releases to maintain sufficient impact. Synthetic gene drives promise more efficient approaches since they can increase in frequency from rare, yet this also allows them to spread across a landscape, which may not always be desired. Between these two extremes are selectively neutral genetic constructs which persist at the frequency they are released, offering the potential for efficient suppression that remains localised. One way to achieve this would be to have perfect balance, at all construct frequencies, between gene drive increasing frequency and selection decreasing it. Here we describe a way to create this balance involving a toxin-antidote genetic construct that causes recessive lethality, encodes a genomic editor that makes dominant lethal edits in the genome, and provides protection against the action or consequences of the editing. Computer modelling shows that this design can be 100-fold more efficient than sterile males, increasing to 1000-fold more when released alongside a genetic booster. We describe designs for CRISPR-based molecular construction, including options that avoid using recoded genes as antidotes.

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