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June 26 (UPI) – The researchers used the CRISPR-Cas9 gene edition to reduce the symptoms of autism in mice with a form of the most common cause of an autism spectrum disorder, or ASD.
Scientists at the University of California at Berkeley have developed a method of gene editing with CRISPR by delivering the Cas9 enzyme that cuts DNA into the brain, reducing the repetitive behavior characteristic of the Fragile X syndrome. The results were published Monday in the journal Nature Biomedical Engineering.
FXS, a common form of ASD, occurs in about 1 in 4,000 men and 1 in 8,000 women.
The researchers used the CRISPR-Gold method that they developed to edit the gene for a neurotransmitter receptor linked to repetitive behaviors, a common symptom of autism. Based on the study, researchers believe that they may be able to apply the method to other aspects of autism, as well as other diseases like Huntington's disease or other polygenic conditions.
"There are still no treatments or cures for autism, and many clinical trials of small molecule therapies targeting the proteins responsible for autism have failed," says the author. Dr. Hye Young Lee, Assistant Professor of Cellular and Integrative Physiology at the University. of the Texas Health Science Center in San Antonio, said in a press release. "It is the first case where we have been able to edit a causative gene for autism in the brain and show the rescue of behavioral symptoms."
The significant difference in this use of CRISPR, said Niren Murthy, inventor of CRISPR-Gold, professor of bioengineering at UC Berkeley, is that researchers have injected it directly into the brain and that it has worked.
"It's the first time anyone has shown it with a non-viral delivery," said Murthy.
Other researchers have inserted genes for Cas9 into neurons via viruses, but as the gene continues to express Cas9 enzyme, other genes are cut at random. With CRISPR-Gold, it transports the Cas9 complex directly into cells, makes a few cuts and then disappears.
"If you inject CRISPR DNA using a virus, you can not control the amount of Cas9 protein and the guide RNA are expressed, so the injection 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 want to inject and that probably minimizes the side effects of using CRISPR, for example out-of-target effects."
For the study, the researchers injected CRISPR-Gold carrying the Cas9 complex into the striatum of the mouse brain, a region known for mediating habit formation – including repetitive behaviors.
The researchers targeted an excitatory receptor called the metabotropic glutamate receptor 5, or mGluR5, which is involved in communication between neurons and is known to be dysregulated in FXS.
"Prior to this experiment, we did not know if the mGluR5 receptor in the striatum was specifically involved in exaggerated repetitive behavior, it is an important biological finding of our study," said Lee.
The researchers say that they reduced the number of receptor proteins in mice by about half, as about 50 percent of the mGluR5 genes in the striatum were published. This allowed the mice to show 30% fewer obsessive digs and 70% fewer jumps.
The researchers are currently developing CRISPR-Gold particles to inject directly into the central nervous system through the spinal cord, eliminating the need to open the skull and inject them directly into the brain.
Lee believes the method can be used to treat conditions that include opioid addiction, neuropathic pain, schizophrenia and epileptic seizures, as well as autism, among other conditions.
"CRISPR-Gold can be used to treat a variety of genetic diseases, such as Huntington's disease," Lee said.
"But it is not limited to monogenic diseases, it can also be used against polygenic diseases, once we understand the entire network of genes involved."
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