Scientist Dr. Hye Young Lee and her team have found a new way to use the gene editing technology CRISPR and recently published their findings in the July issue ofNature Biomedical Engineering.

“This study shows the first time demonstration of rescuing autistic symptoms using gene editing in autism mouse model. On top of that, we used a non-viral way to do it which supports the potential therapeutic treatment for brain disorders,” explained Dr. Lee, assistant professor in the Department of Cellular and Integrative Physiology at UT Health San Antonio.

Dr. Lee along with a team of researchers from the University of California, Berkeley used nanoparticles carriers to inject a gene-editing enzyme called Cas9 into the striatum, a brain region associated with formation of habits and edited the gene to reduce the repetitive behavior characteristic of fragile X syndrome (FXS), which is an inherited cause of autism spectrum disorders.

Enzymes are proteins that trigger biochemical reactions. “The enzyme we used, Cas9, is like a pair of scissors,” said Dr. Lee. “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.

The team is believed to be the first to successfully edit a causal gene for autism in the brain and diminish symptoms.

“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 precisely 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.”

CRISPR-Gold consists of gold nanoparticles covered by DNA chains that hold the Cas9 molecules in place. The delivery package used in the UT Health San Antonio study also contains ribonucleic acid (RNA) guidance to cause the nanoparticles to act like smart missiles homing in on the excitatory mGluR5 molecule.

Dr. Lee is passionate about her research because she enjoys learning how brain works and what makes brain disorders.

“Being a scientist is fun. I also want to contribute to the advance in our understanding about autism and also to the therapeutic treatment,” Dr. Lee said “Our lab works hard since we are very motivated.”

Dr. Lee will continue to work to optimize the CRISPR-Nanoparticle delivery method by collaborating with Dr. Niren Murthy’s team at UC Berkeley. They will also be looking at a wider effect in the brain by testing other injection ways such as intrathecal injection.

“Our research was very demanding from both autism research aspect and gene-editing tool aspect. So, this study happened to be very impactful. I am delighted by the fact that I can be a contribution to the scientific society by sharing more information on what we can do with gene-editing.”

Coauthors from UT Health San Antonio’s Joe R. & Teresa Lozano Long School of Medicine also included Robert Brenner, Ph.D., associate professor of cellular and integrative physiology; Vladislav Bugay, Ph.D., postdoctoral fellow in the Brenner laboratory; Shree Panda, research assistant; and Rodrigo Gonzales-Rojas of Health Careers High School in San Antonio’s Northside Independent School District.

In addition to the Rising STARs award, Dr. Hye Young Lee is a recipient of grants from the San Antonio Life Sciences Institute of UT Health San Antonio and The University of Texas at San Antonio, the Center for Biomedical Neuroscience at UT Health San Antonio, the Brain & Behavior Research Foundation, the Simons Foundation Autism Research Initiative (SFARI) and the San Antonio Area Foundation.

Please find news about Lee lab at www.hyeyoungleelab.org/news