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CRISPR could lead to gene-editing fix for a form of male infertility

Infertile male mice have fathered offspring after their condition was fixed by CRISPR – an approach that could help many couples with fertility problems
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CRISPR might help fix a form of male infertility
Dino Citraro/Moment Select/Getty

Male mice with a mutation that prevented them producing any sperm have fathered offspring the natural way after a team in China fixed their infertility by CRISPR genome editing.

The technique could one day help many infertile men around the world. “I think this study is very exciting,” says Sarah Vij, a male infertility specialist at Cleveland Clinic Foundation in the US, who was not involved in the work. “Most of us think this is the future for these men.”

There are several known genetic mutations that prevent the stem cells in the testes giving rise to healthy sperm. Some men still have non-moving sperm cells in the testes that can be surgically extracted and injected into eggs. But this doesn’t always work, and children created this way risk inheriting the mutation that made their father infertile.

So for decades biologists have been exploring ways of correcting these mutations. In 2015, for instance, one team showed that they could restore the ability of mice stem cells to produce healthy sperm by using CRISPR genome editing to correct the underlying genetic mutation.

Healthy offspring

Now Xiaoyu Li’s team at the Affiliated Hospital of Guangdong Medical University has taken this work a step further by taking stem cells from a mouse, correcting the mutation and implanting them back in the same mouse. Four months later, the mice mated with females, and 9 out of 11 fathered healthy offspring.

However, there is still a way to go before trying this in people. The biggest obstacle, says reproductive expert Geert Hamer of the University of Amsterdam, is that there is no reliable way of isolating human sperm stem cells.

Another issue is that in some cases it might be necessary to kill off the mutant stem cells in the testes to prevent them competing with the corrected ones, Hamer says. This would likely require chemotherapy or radiation, so developing lab-grown sperm and using it for IVF might be a safer approach.

Around 1 per cent of men suffer from non-obstructive azoospermia, as the condition is known. Only a small fraction of these cases can currently be pinned on specific genetic mutations, but that still adds up to a lot of men globally. And it may be that many – perhaps even most – of the other cases are due to as-yet undiscovered mutations, Vij says.

Justified use

Vij thinks using germline genome editing to treat infertility would be entirely justified. But the birth of lots of CRISPRed kids would also open the door to other uses, she says.

In their study, Li’s team write that they believe their technique “will play a key role in getting human offspring without genetic disease in the near future”.

“It’s a slippery slope, right? All of a sudden you are doing a tremendous amount of gene-editing, creating scientifically made babies,” Vij says. “Once you’re able to do this then you are able to edit for all sorts of things.”

While germline genome editing – altering the DNA of eggs or sperm –  is often presented as a way of preventing genetic disorders such as cystic fibrosis, virtually all such diseases are already preventable by screening IVF embryos before implantation. There are only a few exceptions.

For instance, some deaf couples’ only chance of having hearing children of their own is to use gene editing to correct the mutation. In July, èƵ revealed that a biologist in Russia says he has found five deaf couples there who want to use gene-editing for this purpose.

Stem Cell Research & Therapy

Topics: CRISPR