World first trial to eradicate mice through gene modification

Mouse populations could be eradicated in some areas through new gene modification technology to render female mice infertile. 

The technology – called t-CRISPR – was previously developed to target malaria-transmitting mosquitoes. This is the first proof of concept for its use as a mammalian genetic biocontrol tool targeting house mice, which is an invasive pest in Australia.

In time, it could be used to control rodents on islands and landmasses where they cause widespread destruction.

The research, published in Proceedings of the National Academy of Sciences, is the first time t-CRISPR has been successfully tested on mammals in a laboratory setting, according to senior author Professor Paul Thomas.

Computer modelling conducted by the team suggests about 250 gene-modified mice could eradicate an island population of 200,000 mice in around 20 years.

“We have had mouse plagues in Australia for 150 years and existing controls, like baits, cause inhumane death and are expensive and labour intensive to deploy,” says Thomas, who works across the University of Adelaide and the South Australian Health and Medical Research Institute.

“This is the first time that a new genetic tool has been identified to suppress invasive mouse populations by inducing female infertility.

“The t-CRISPR approach uses DNA editing technology to make alterations to a female fertility gene. Once the population is saturated with the genetic modification, all the females that are generated will be infertile.”

Despite its promise as a new pest control, the researchers are aware there will be ethical and social concerns around eradicating mice, and has taken these into consideration while developing the gene drive, although similar research in relation to feral cats has found favour.

“The use of t-CRISPR technology provides a humane approach to controlling invasive mice without the release of toxins into the environment,” says co-first author and PhD student working on the project Luke Gierus.

“We are also working on strategies to prevent failed eradication due to the emergence of gene drive resistance in the target population.”

Gene modification could be expanded to other small pests.

The research team worked closely with Australia’s national science agency CSIRO, the Centre for Invasive Species Solutions, the Genetic Biocontrol for Invasive Rodents consortium and the US Department of Agriculture, to consider next steps towards safely implementing the new technology.

Although the technology may be limited in larger mammals with longer generation times like cats and foxes, CSIRO Group Leader for Environmental Mitigation and Resilience Dr Owain Edwards says t-CRISPR could be feasible in rats and rabbits.

“This particular prototype has been designed to be highly specific for mice, but it is also evidence that gene drives can be developed against other invasive pest animals,” Edwards says.

“As part of this research, we conduct the safety assessments for this technology to the highest standards. Because this is the first prototype for a vertebrate gene drive, interested stakeholders will include many from the international community.”

Genetic biocontrol through t-CRISPR avoids the problem of cross contamination with other species.

“This system is species specific,” says Thomas.

“This is because house mice only breed with each other and not with native mice, preventing the spread of this system between species.

“This is one of the advantages of a genetic biocontrol approach, compared with current control strategies such as bait and traps, that can impact native mice.”

Thomas says there have not yet been any field trials but the research groups in the US have simulated natural environments where enclosure trials could potentially be performed.

“This will require significant funding and we are currently exploring options for that,” he says.

“Enclosure trials would also enable us to further investigate various safety mechanisms which limit the gene drive activity to the target population – for example tailoring this system to target specific populations in specific regions, like targeting an island population but not the nearby mainland animals.”

 

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