image: This artist's concept shows two nanoparticles coming into the brain (at top) while a pair of scissors cuts at bottom right. This illustrates UT Health San Antonio scientists' use of gene editing to cut DNA at a precise location to reduce autism symptoms in mice with fragile X syndrome.
Scientists at UT Health San Antonio have edited a gene in the brain to decrease the repetitive behaviors of mice with fragile X syndrome, which is an inherited cause of autism spectrum disorders. The study is described in the July issue of Nature Biomedical Engineering.
The San Antonio researchers, who included study leader Hye Young Lee, Ph.D, and first author Bumwhee Lee, Ph.D., used nanoparticle carriers developed in California to inject a gene-editing enzyme called Cas9 into the striatum, a brain region associated with formation of habits.
Enzymes are proteins that trigger biochemical reactions. "The enzyme we used, Cas9, is like a pair of scissors," said Dr. Hye Young Lee, assistant professor in the Department of Cellular and Integrative Physiology at UT Health San Antonio. "We were able to cut the genetic blueprint, DNA, at a location that causes the exaggerated repetitive behaviors."
The researchers targeted Cas9 at a molecule called mGluR5 that is excitatory--it increases communications between neurons. The approach worked. The rodents' digging behavior slowed by 30 percent and the leaping behavior was reduced by 70 percent. In the process, the research revealed valuable information about mGluR5's function, Dr. Lee said.
Groundbreaking
The team is believed to be the first to successfully edit a causal gene for autism in the brain and diminish symptoms, the authors wrote. Significantly, the effect is permanent, Dr. Lee said.
"The approach can also be used to treat other diseases if we know the gene target," she said. This includes many neurological diseases such as epilepsy, and the brain cancer glioblastoma."
The study is also one of the first in the scientific literature to employ a safer, non-viral approach of Cas9 delivery to a brain region.
"Previous attempts by other groups used viral carriers to convey Cas9, which has potential problems because the virus can't be programmed to stop working," said Dr. Bumwhee Lee, postdoctoral fellow in Dr. Hye Young Lee's laboratory. "This can result in serious immune reactions and cell toxicity."