Researchers at the Francis Crick Institute and the University of Kent have employed gene-editing technology to create single-sex litters of mice with 100 percent efficiency, a breakthrough that could lead to the dramatic reduction of culling in both medical and agricultural settings.
The work, published in Nature Communications, approaches the CRISPR-Cas9 gene-editing technique in a clever way. The Cas9 enzyme can cut bits of DNA and is an incredible tool. Here, the team placed one element of this system on the father’s X or Y chromosome, and the other on the mother's X chromosomes.
When an embryo formed, Cas9 was made whole again and would target the Top1 gene – which is important for DNA replication and repair – halting the development of the embryo.
“This method works as we split the genome editing process in half, between a male and female, and it is only when the two halves meet in an embryo through breeding, that it is activated. Embryos with both halves cannot develop beyond very early cell stages,” first author Dr Charlotte Douglas said in a statement.
“We’ve also shown this process works successfully in different combinations – introducing either the Cas9 or the guide RNA elements on to the mother’s or father’s chromosomes.”
The gene-editing had no harmful side effects for the surviving offspring. Also, due to the high number of eggs produced by mice, this method didn’t halve the size of the litters. The single-sex litters were between 61 and 72 percent the size of the control litters.
The breakthrough could be used in medical settings where there is a need to have a single-sex population. But also in farms where animals of the “wrong” sex are culled usually after birth. But there’s a lot of work still to do to actually employ it beyond a lab.
“The implications of this work are potentially far-reaching when it comes to improving animal welfare, but should be considered at ethical and regulatory levels,” Peter Ellis, co-author and senior lecturer in molecular genetics and reproduction at the University of Kent, added.
“In particular, before any potential use in agriculture, there would need to be extensive public conversation and debate, as well as changes to legislation. On the scientific side, there is also much work to be done over a number of years. Further research is needed, first to develop the particular gene editing toolkits for different species, and then to check they are safe and effective.”