CRISPR Gene-Drive Tested on Mammals for the First Time in History
With the rise of CRISPR technologies, we were talking about the potential concerns of RNA-guided gene drives back in 2014. Now, scientists are applying the controversial technology to mammals for the first time.
In a reprint posted to bioRxiv, researchers at the University of California, San Diego describe the use of gene drives in laboratory rodents to create complex genetic models. The technique offers a way in which multiple genes in mice can be altered to model complex multigenic human diseases.
This differs from the focus of previous work using gene drives in mosquitos, where the system is being used to force the expression of genes that affect its development negatively in hope to eradicate the disease-carrying species, Aedes aegypti. However, the research does contribute to the ongoing debate about the application of CRISPR/Cas9 gene drives to combat invasive rodent populations in island communities.
The technique, in theory, could help to kill off a species of invasive rodent pests by, for example, ensuring that all offspring of the rodents would be born with detrimental genes such as those that result in infertility or even death. However, this latest study outlines many inconsistencies and multiple technological hurdles that must be overcome before even considering releasing the technique into the wild.
For example, when Kim Cooper, developmental geneticist at the University of California, San Diego, and her team attempted to use the gene drives in mice embryos, the technique only worked in female mice and even then, the mutation wasn’t always copied correctly.
Based on the results, her team estimated that this could lead to a mutation being transmitted to about 73% of a female mouse’s offspring, on average, instead of the usual 50% for most genes operating under the usual rules of inheritance. Cooper declined to comment on her team’s work, because it has not yet been published in a peer-reviewed journal.
Tony Nolan, a molecular biologist at Imperial College London who is part of a team developing gene drives in malaria-carrying mosquitoes told Nature that he is excited to see that gene drives can, at least, work in rodents. Even if the technology doesn’t become an eradication tool, it could help to produce transgenic lab animals that model diseases caused by multiple mutations more efficiently than existing technologies, he says.
Other researchers agree that the study is important, but say it also shows just how long the technology has to go in rodents. “Could you imagine this gene drive in the wild? That’s not going to happen,” says Gaétan Burgio, a geneticist who works on CRISPR at Australia National University in Canberra. The relatively low efficiency of the technique means it would take many generations for the gene drive to spread through an entire rodent population, leaving ample time for species to evolve resistance to the gene drive.