ORCID Profile
0000-0002-3152-9682
Current Organisation
University of Adelaide
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Publisher: Cold Spring Harbor Laboratory
Date: 31-05-2022
DOI: 10.1101/2022.05.31.494104
Abstract: Invasive rodents, including house mice, are a major cause of environmental damage and bio ersity loss, particularly in island ecosystems. Eradication can be achieved through the distribution of rodenticide, but this approach is expensive to apply at scale, can have negative impacts (e.g. on non-target species, or through contamination), has animal ethics concerns, and has restrictions on where it can be used. Gene drives, which exhibit biased inheritance, have been proposed as a next generation strategy to control invasive alien pests and disease vectors. However, synthetic gene drives including CRISPR homing drives have proven to be technically challenging to develop in mice. The t haplotype is a naturally-occurring segregation distortion locus with highly biased transmission from heterozygous males. Here we propose a novel gene drive strategy for population suppression, t CRISPR , that leverages t haplotype bias and an embedded SpCas9/gRNA transgene to spread inactivating mutations in a haplosufficient female fertility gene. Using spatially explicit in idual-based in silico modelling, we show that polyandry, sperm competition, dispersal, and transmission bias are critical factors for t CRISPR -mediated population suppression. Modelling of realistic parameter values indicates that t CRISPR can eradicate an island population of 200,000 mice while the unmodified t haplotype fails under the same conditions. We also demonstrate feasibility of this approach by engineering t CRISPR mice in a safe split drive format. t CRISPR mice exhibit high transmission of the modified t haplotype, and efficient generation and transmission of inactivating mutations in a recessive female fertility gene, crucially, at levels for which the modelling predicts that population eradication can occur. This is the first ex le of a feasible gene drive system for invasive alien rodent population control.
Publisher: Proceedings of the National Academy of Sciences
Date: 08-11-2022
Abstract: Invasive rodents are a major cause of environmental damage and bio ersity loss, particularly on islands. Unlike insects, genetic biocontrol strategies including population-suppressing gene drives with biased inheritance have not been developed in mice. Here, we demonstrate a gene drive strategy ( t CRISPR ) that leverages super-Mendelian transmission of the t haplotype to spread inactivating mutations in a haplosufficient female fertility gene ( Prl ). Using spatially explicit in idual-based in silico modeling, we show that t CRISPR can eradicate island populations under a range of realistic field-based parameter values. We also engineer transgenic t CRISPR mice that, crucially, exhibit biased transmission of the modified t haplotype and Prl mutations at levels our modeling predicts would be sufficient for eradication. This is an ex le of a feasible gene drive system for invasive alien rodent population control.
Publisher: Springer US
Date: 2022
DOI: 10.1007/978-1-0716-2301-5_11
Abstract: Gene drives are genetic elements that are transmitted to greater than 50% of offspring and have potential for population modification or suppression. While gene drives are known to occur naturally, the recent emergence of CRISPR-Cas9 genome-editing technology has enabled generation of synthetic gene drives in a range of organisms including mosquitos, flies, and yeast. For ex le, studies in Anopheles mosquitos have demonstrated >95% transmission of CRISPR-engineered gene drive constructs, providing a possible strategy for malaria control. Recently published studies have also indicated that it may be possible to develop gene drive technology in invasive rodents such as mice. Here, we discuss the prospects for gene drive development in mice, including synthetic "homing drive" and X-shredder strategies as well as modifications of the naturally occurring t haplotype. We also provide detailed protocols for generation of gene drive mice through incorporation of plasmid-based transgenes in a targeted and non-targeted manner. Importantly, these protocols can be used for generating transgenic mice for any project that requires insertion of kilobase-scale transgenes such as knock-in of fluorescent reporters, gene swaps, overexpression/ectopic expression studies, and conditional "floxed" alleles.
No related grants have been discovered for Luke Gierus.