A team of scientists have used the CRISPR Cas-9 gene editing technology to reduce autism symptoms in mice, according to a study published in the journal Nature Biomedical Engineering on Monday. The mice that were tested had a form of fragile X syndrome, a common cause of autism spectrum disorder.

The researchers used a gold nanoparticle to transport the DNA-cutting Cas9 enzyme into the brain of the mice to edit the gene for a neurotransmitter receptor called mGluR5, which led to a reduction in repetitive behaviors characteristic of fragile X syndrome. Scientists at the University of California Berkeley developed the technique, called CRISPR-Gold, which was used the get the Cas9 enzyme into the brain.

“There are no treatments or cures for autism yet, and many of the clinical trials of small-molecule treatments targeting proteins that cause autism have failed,” Hye Young Lee, an assistant professor at the University of Texas Health Science Center at San Antonio and study leader, to UC Berkeley’s media relations office.


“This is the first case where we were able to edit a causal gene for autism in the brain and show rescue of the behavioral symptoms,” said Young.

Over the course of two years, the researchers tested hundreds of mice, monitoring behaviors like digging and burying, to see how they responded to gene editing. For the digging and burying experiment, the researchers added marbles to their bedding to monitor how much of the activity they did.

Mice like to dig, but the ones with fragile X syndrome dig and bury marbles “obsessively,” according to a video made about the study, continuously digging up and burying the marbles in their cage. But once those mice had their mGluR5 neurotransmitter disabled by the Cas-9 enzyme, they significantly reduced the amount of digging and burying they were doing.




“It’s known that in autism one of the behavioral problems is that you have repetitive behaviors,” said Niren Murthy, a UC Berkeley professor of bioengineering who invented CRISPR-Gold and was a co-author on Lee’s study. “What’s interesting is that some of the repetitive behaviors are caused by the striatum [part of the brain known for regulating habit formation]….We were only able to effect the behaviors that were striatum-dependent, like jumping and marble burying.”


There were other behaviors, like line crossing, that are regulated by the hippocampus, a part of the brain that plays an important role in spatial, short-term and long-term memory, that they were not able to effect.

Still, the researchers were able to achieve a reduction of some of the symptoms by only editing the genes of part of the brain. “That’s significant because you’re not going to get a lot of the toxicity that’s generated from globally inhibiting” neurons in the brain, Murthy said.

Another significant finding from the study, Murthy said, is that the method used to transport the Cas-9 enzyme into the brain, CRISPR-Gold, did not require introducing a virus into the body.

“No one had figured out how to deliver the gene-editing enzyme into the brain…non-virally,” Murthy said. “So that was a big unsolved challenge and one of the things we showed in this paper is that we were able to deliver the gene-editing enzyme non-virally and get therapeutic effects.”

He said that the study shows that it’s possible treat genetic diseases that effect the brain, like Alzheimer’s, Parkinson’s and other types of autism spectrum disorder, by employing local treatments without introducing viruses into the body. Later, he said in an email that disabling the mGluR5 neurotransmitter could have application for treating drug addiction, sending along a 2012 study linking mGluR5 with addiction.

Although the CRISPR-Gold method does not require introduction of virus into the brain, the gold nanoparticle that is used “can potentially accumulate in the brain after multiple injections,” the paper says, which “may prevent CRISPR–Gold from being injected into patients multiple times.”

“However,” Lee and her co-authors wrote in the paper, “a single injection into the brain of an extremely low dose of gold in CRISPR–Gold (2.84 µg kg–1) efficiently rescued [behavioral] deficits in mice, and appears to be well tolerated in the brain.”

Murthy thinks that this method for treating genetic diseases that effect the brain, or even a better form of the CRISPR gene editing technology, could be used in humans in the next few years.

“The strange thing about CRISPR is that everything moves at this incredibly fast pace….The whole field is at such an early stage that it’s likely that we can make delivery vehicles that are much better than CRISPR-Gold,” he said. “But like a non-viral CRISPR delivery strategy for a brain disease should be tested within five years in a human patient.”

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