Chinese Bioengineers Develop Artificial Sperm to Create Armies of Half-Cloned Mice

Scientists at the Chinese Academy of Sciences’ Shanghai Institute for Biological Sciences, led by Li Jinsong, WU Yuxuan of the Institute of Biochemistry and Cell Biology, and YANG Li of CAS-MPG Partner Institute for Computational Biology, have successfully mass produced viable high-quality artificial sperm for the first time.

The research, published in Cell Stem Cell with the title “CRISPR-Cas9-Mediated Genetic Screening in Mice with Haploid Embryonic Stem Cells Carrying a Guide RNA Library,” builds on previous work to create viable artificial mouse sperm that can support full-term embryonic development after being injected into egg cells to create a generation of semi-cloned mice (mice with DNA from both the artificial sperm and the natural egg cells).

However, in previous studies only a few percent of of the fertilized eggs developed into healthy half-cloned mice. Now the researchers found that tweaking two paternally imprinted genes – H19 and Gtl2 – results in much improved generation of mouse pups at a rate of 20 percent.

“We could not believe the results ourselves at first. The method was so simple,” said Li.

Extensive CRISPR-Cas9 Gene Editing of Artificial Sperm

Genetic Modification of Artificial SpermThe scientists used CRISPR-Cas9 gene editing technology to extensively modify specific genes in the artificial sperm and confirmed that the changes were reflected in the half-cloned pups.

The image shows how the combined application of altered expression of two imprinted genes and CRISPR-Cas9-based genome editing allows the efficient and stable generation of gene-modified semi-cloned mice.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) -Cas9 technology permits to cut out sections of DNA and replace them with new ones. In the two-part process, first an RNA “guide” molecule marks the DNA strand to be removed, then a Cas9 protein attaches to the DNA and cuts out the strand, which in some cases can be replaced by a new one.

“Our man-made sperms cells can be used to generate an army of half-cloned mice with ease and efficiency,” Li explained to South China Morning Post.

These half-cloned mice will fight on the frontline in battles against cancer and other genetic health issues.

Li expressed hopes that the new technology could help cure human diseases with emerging genetic therapies, and concerns about the possibility that mass production of sperm would lead to an “ethical crisis” if it was applied to humans.

“A 20 percent rate for healthy breeds may be good enough for experimental animals, but not humans,” said Li. “If it is applied to human sperm it could lead to an 80 per cent death rate or defects at birth.”

It seems likely, however, that a success rate of 20 percent is only a first result that could be very significantly improved upon by future work.

Images from Shanghai Institute for Biological Sciences and Shutterstock.

Giulio Prisco is a freelance writer specialized in science, technology, business and future studies.