CRISPR gene therapy regulates hunger, staves off severe obesity in mice

CRISPR gene editing technologies offer some exciting possibilities for medicine, whether it’s helping to treat ALS, battling the spread of malaria, or potentially providing us with a limitless supply of transplant organs. But gene editing is controversial, too, as evidenced by the recent outcry concerning reports from China that babies had their DNA edited to potentially stop fatal diseases such as HIV, smallpox, and cholera.

That is one reason why a new piece of research from the University of California, San Francisco researchers is so potentially exciting. They have demonstrated how CRISPR therapies can be used to prevent severe obesity in mice. However, they achieved this long-lasting weight control without having to make one single edit to the mice’s genome. The resulting technique could potentially be applied to other types of genetic modification as well.

“We have two copies of each gene: One from each parent,” Nadav Ahituv, professor of Bioengineering and Therapeutic Sciences at UCSF, told Digital Trends. “If one copy has a mutation that makes it non-functional, that will provide only half the RNA and protein from that gene. For some genes, this is perfectly fine, but there are 660 genes where having half [the RNA and protein] leads to human disease. In those cases, you still have one perfectly normal copy that is just giving you RNA and protein levels at 50 percent. What we did here was target that normal copy, and squeeze out more RNA and protein from it by increasing the levels it generates. We specifically target that gene by taking advantage of CRISPR … but use a mutant form of CRISPR that is not able to cut DNA, just target it.”

The team selected obesity as their model to see if they could resolve it by targeting the one normal copy of both of two genes critical for regulating hunger. These genes are frequently found to be mutated in severely obese individuals. When one of these the copies of these genes is disabled, the remaining copy has to carry all the workload. As such, the signal it sends — telling the individual that they have eaten enough — is not sufficiently loud. The result is that the person is subject to an unceasing appetite.

Having worked in their experiment with mice, the researchers believe similar approaches could work in human trials. “However, many more experiments and time will be needed before this might be safely used in the clinic,” Ahituv said. “This should only be introduced into patients after proper experiments, clinical trials and human protocol approvals are in place.”

A paper describing the work was recently published in the journal Science.