Chinese scientists edit genes to produce artificial sperm capable of creating 'army of half-cloned mice'
Scientists in mainland China have successfully mass produced high-quality artificial sperm for the first time.
The man-made sperm do not have tails and cannot swim, looking more like eggs than natural sperm, but they can fertilise an egg and pass on genetic information to potential offspring, according to a paper published in the journal Cell Stem Cell
"Our man-made sperms cells can be used to generate an army of half-cloned mice with ease and efficiency. These half-cloned mice will fight on the frontline in battles against cancer and other genetic health issues,” said professor Li Jinsong, lead scientist on the project with the Chinese Academy of Sciences’ Shanghai Institute for Biological Sciences.
The researchers injected an artificial sperm into a natural egg. The resulting mouse was half-clone, with 50 per cent of its genes coming from one of thousands of sperm cultured in a test dish.
A powerful gene-editing tool called CRISPR-Cas9 has allowed the researchers to add, disrupt or change the sequence of specific genes in the sperm. Using CRISPR-Cas9 together with the man-made sperm, the scientists could now explore the function of many genes simultaneously, while in the past it could only be done one at a time.
Man-made sperm have been produced by scientists in labs around the world for years, but the output remained scarce. Each sperm was made from a stem cell, and the stem cells, taken mainly from embryos, were always in short supply.
“We thought it would be great if the sperm could be cultured to multiply endlessly like normal cells,” Li said.
They achieved this by putting the sperm in an egg with the nucleus removed, which would turn into a haploid embryonic stem cell with functions similar to sperm. In 2012 the team reported the first mass production of man-made sperm with this technology.
But quality of these sperm was a problem. For instance, only about 2 per cent of the fertilised eggs could develop into healthy half-cloned mice.
In their new paper, Li’s team reported an improved method which increased the proportion of healthy mice to over 20 per cent.
“We could not believe the results ourselves at first. The method was so simple,” Li said.
To confirm their discovery the team conducted some extensive editing on the sperm’s genes with the CRISPR-Cas9 tool and found the changes were reflected in the mutations on half-cloned breeds.
The study had prompted new issues. For instance, scientists were still unclear about the exact function of the genes they knocked out, H19 and Gtl2, in the man-made sperm and how they affect embryonic development.
Though he hoped the new technology could help cure human diseases under emerging genetic therapies, Li said the mass production of sperm would lead to an "ethical crisis" if it was applied to humans.
“A 20 per cent rate for healthy breeds may be good enough for experimental animals, but not humans. If it is applied to human sperm it could lead to an 80 per cent death rate or defects at birth.”