MIT Researcher Develops CRISPR Gene Therapy for Rare Childhood Epilepsy

Shannon Knight was in high school when she walked past an open classroom door at the University of Illinois Chicago and saw something that stopped her cold: a human brain, held in someone's hands. She and her sister backpedaled into the room. The brain belonged to a patient who had died of Alzheimer's. Holding it, Knight felt the weight of it—not just physical, but existential. A man's entire life of memory and choice and feeling had been contained in this organ. Something shifted in her that day. She decided then that she wanted to understand the brain.

Now, six years into her doctoral work at MIT's McGovern Institute for Brain Research, Knight is pursuing that childhood fascination through a specific and urgent problem: a rare genetic disorder called SYNGAP1 haploinsufficiency that causes seizures in infants as young as four months old. The disorder stems from a mutation that disables one of two copies of the SYNGAP1 gene, which is critical for how the brain develops and how neurons communicate with each other. Children with the condition face not only seizures but intellectual disabilities, feeding and sleep problems, and movement difficulties. As they grow older, the seizures often become resistant to the anti-seizure medications that initially help. There is no cure, only symptom management that gradually fails.

Knight is working to change that using CRISPR, the gene-editing tool that has transformed molecular biology over the past decade. Rather than trying to suppress seizures after they occur, her approach targets the genetic root of the problem itself. She is developing a gene therapy that could, in theory, repair the broken gene and prevent the cascade of neurological damage from starting. Early results in mice carrying a version of the disorder are striking: the therapy has eliminated seizures and reversed the behavioral problems associated with the condition.

The path to this work was not straightforward. At Bowdoin College, Knight majored in neuroscience and completed an honors thesis on neuron regeneration in crickets. She had considered medical school but found that research drew her more powerfully. After graduation, she spent two years at Harvard's Perrimon Lab, where she first encountered CRISPR and learned to apply it in fruit fly models. She published papers and built her credentials. When she arrived at MIT to study under Professor Guoping Feng, she initially focused on a different rare disorder—Phelan-McDermid Syndrome, caused by a deletion on chromosome 22. That work has advanced far enough that a gene therapy based on it is now in clinical trials with human patients. Knight is now applying the same rigorous pathway to SYNGAP1, with the goal of eventually reaching FDA approval and human testing.

What drives her, she says, is a commitment to what she calls "leading science with empathy." SYNGAP1 disorder is extraordinarily rare, affecting only one to four children per ten thousand. It is easy for researchers to overlook such small populations in favor of diseases that affect millions. But Knight has chosen to focus her doctoral years on these invisible patients. She does not have a personal connection to anyone with the disorder, but she thinks often about people who feel unseen by the systems meant to help them. She wanted her work to matter for them.

Beyond the lab, Knight has become a teacher. She leads the laboratory section of MIT's Experimental Molecular Neurobiology course, walking students through the process of identifying specific proteins in neurons and designing experiments that move from cell cultures to living mouse brains. She received the Goodwin Medal in 2025 for her teaching excellence. Students have told her since that the course was among their favorites. Her advisor, Guoping Feng, describes her as emblematic of the graduate students at MIT who are driven not by abstract ambition but by a genuine desire to use cutting-edge science to help people living with devastating conditions.

The work is still in early stages. Mouse models are not humans. The path from promising preclinical results to an approved therapy is long and uncertain. But the Rare Brain Disorders Nexus, an MIT initiative launched in fall 2025, is accelerating Knight's research by bringing together labs and resources focused on genetic disorders that affect small populations. If the SYNGAP1 gene therapy follows the trajectory of the Phelan-McDermid work, clinical trials could begin within years. For the families of children with SYNGAP1 disorder—children who seize and struggle and whose seizures grow resistant to medication—that timeline represents something that did not exist before: the possibility of a cure.