A study published in Scientific Reports explores a novel combination of CRISPR‑based gene drives to control invasive gray squirrel – Sciurus carolinensis – in the UK.
"Burning the library of life"
Biodiversity refers to the extent of the variety of life that is found on planet Earth – and it is currently under threat. Changes in biodiversity have been flagged as "surpassing safe limits" for several years, and world leaders and scientists across the globe are consequently exploring different ways to address the crisis.
Invasive species, defined by National Geographic as "an organism that is not indigenous, or native, to a particular area", threaten planet Earth's biodiversity to an even greater extent than climate change. The Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) Global Assessment Report found that the number of invasive species per country have risen by ~70% since 1970 across 21 countries that were included in the report.
An example of an invasive species is the gray squirrel Sciurus carolinensis found in the UK, which outcompetes the native red squirrel for resources and habitats and carries diseases that are not pathogenic to themselves but can kill red squirrels.
Expanding the conservation toolbox with gene drives
One way to tackle invasive species – and therefore biodiversity issues – is the use of genetic engineering principles and techniques such as gene drives. This is not a novel research area, rather one that has been dramatically enhanced by the recent discovery and evolution of CRISPR-based gene-editing technology.
Gene drive is a broad term that Dr Jennifer Baltzegar, a population geneticist at North Carolina State University, summarizes as "a selfish genetic construct that spreads rapidly through a population […] It is found at a higher ration in the offspring than you would expect for typical Mendelian inheritance." Desirable genes can be added to these constructs, such as genes that induce infertility in females, thereby controlling population size.
Teach Me in 10 – Gene Drive Research With Dr Jennifer Baltzegar.
The majority of gene drive work conducted to date has focused on mosquitoes and researchers are still working to refine methods and address technical challenges, such as genetic resistance.
New research by Nicky Faber and colleagues at Wageningen has modeled the effectiveness of combining three gene drive technologies – collectively known as HD-ClvR – to suppress the invasive gray squirrel.
"HD-ClvR combats resistance allele formation by combining a homing gene drive with a cleave-and-rescue gene drive. The inclusion of a self-limiting daisyfield gene drive allows for controllable localization based on animal supplementation. We use both randomly mating and spatial models to simulate this strategy," the authors write in the study, published in Scientific Reports.1
A valuable tool in the conservation toolbox?
The modeling work suggests that HD-ClvR would be a suitable method for controlling the gray squirrel population, the authors write: "HD-ClvR overcomes an important trade-off in current homing gene drive designs: the trade-off between resistance allele formation and gene drive efficiency. This strategy benefits from the efficiency of a homing gene drive and the evolutionary stability of cleave-and-rescue gene drive."
"The authors conclude that such gene drives could potentially be very effective if they could be built and provide some pointers as to how to build them, though that remains a significant challenge," – Luke Alphey.
It is important to note that the research is solely computer-based and did not utilize animals. In reality, the implementation of gene drives for gray squirrel population control would be "quite a long-term project", according to Professor Luke Alphey, group leader in Arthropod Genetics at The Pirbright Institute.
There are many research challenges ahead for this field of work, explained Tony Nolan, senior lecturer at the Liverpool School of Tropical Medicine: "The challenge will be in translating these elements from theory into practical testing in the laboratory, which will be no trivial exercise. Demonstration of its practical feasibility would be a significant milestone."
Furthermore, there are societal and ethical implications to consider when adopting genetic engineering methods to intervene with populations. "Regulatory approval and public acceptance would obviously be essential before any actual use of such technology – that is a long way off," said Nolan. Nonetheless, he states that the work indicates gene drives might be a valuable tool in the "conservation toolbox" one day.
1. Faber NR, McFarlane GR, Gaynor RC, Pocrnic I, Whitelaw CBA, Gorjanc G. Novel combination of CRISPR-based gene drives eliminates resistance and localises spread. Scientific Reports. 2021;11(1):3719. doi:10.1038/s41598-021-83239-4.