Scientists have used CRISPR-Cas9 gene editing to lessen some autism symptoms in mice with a form of fragile X syndrome (FXS), the most common known single-gene cause of autism spectrum disorder (ASD).

Employing gold nanoparticles to deliver the DNA-cutting Cas9 enzyme into the brain—a technique developed at the University of California, Berkeley, and called CRISPR-Gold—the researchers were able to edit the gene for a neurotransmitter receptor and reduce the repetitive behavior characteristic of FXS.

Because exaggerated repetitive behaviors are common features in ASDs, the efficient reduction of these behaviors in FXS mouse models demonstrates the potential application of this technique to other types of autism for which the genetic cause is known, the researchers say.

“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,” said study leader Hye Young Lee, an assistant professor of cellular and integrative physiology at the University of Texas Health Science Center at San Antonio. “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.”

According to the researchers, CRISPR-Gold has many advantages over other means of getting Cas9 into the body, such as using viruses.

“The really compelling thing about this paper is that Hye Young was able to show that if you injected CRISPR-Gold into the brain, you could knock out disease-causing genes and actually see fairly significant behavioral changes,” said CRISPR-Gold inventor Niren Murthy, a UC Berkeley professor of bioengineering. “This is the first time anyone had ever shown that with non-viral delivery.”

Those with ASDs have problems interacting with other people as well as exaggerated repetitive behavior, such as rocking and flapping. While ASD appears to have various causes, including multiple genetic mutations, single-gene disorders like FXS are a simpler way of exploring the causes and potential treatments. While ASD affects more than 1% of all children, FXS is rare, occurring in one of every 4,000 boys and 6,000 girls.

The results will be published online June 25 in the monthly journal Nature Biomedical Engineering.

The new study is the first demonstration that Cas9 protein can be ferried into the brain to knock out a gene and have therapeutic effects. While other researchers have inserted genes for Cas9 into neurons via viruses like the adeno-associated virus, problems arise because the gene keeps expressing the Cas9 enzyme, leading to the random cutting of other genes. CRISPR-Gold carries the Cas9 complex itself—purified Cas9 protein and guide RNA—directly into cells, where it cuts a few times and then disappears.

“If you inject CRISPR DNA using a virus, you can’t control how much Cas9 protein and guide RNA are expressed, so injecting it via a virus has a potential problem,” Lee said. “I think the CRISPR-Gold method is very cool because we can control the amount we wish to inject and that probably minimizes the side effects of using CRISPR, for example off-target effects.”

The technique opens the door to treating conditions ranging from opioid addiction and neuropathic pain to schizophrenia and epileptic seizures, Murthy said.