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MIT Researcher Develops CRISPR Therapy for Rare Epilepsy

Doctoral candidate Shannon Knight is testing a gene therapy targeting SYNGAP1 haploinsufficiency, a rare disorder causing medication-resistant childhood seizures.

WHAT YOU NEED TO KNOW
  • Shannon Knight is developing a CRISPR-based therapy at MIT for SYNGAP1 haploinsufficiency, which affects 1 to 4 out of every 10,000 children.
  • Early mouse model testing of the therapy showed alleviation of seizures and behavioral phenotypes.
  • The research builds on Guoping Feng's earlier Phelan-McDermid syndrome gene therapy work, which is now in clinical trials.
  • The project is supported by the Rare Brain Disorders Nexus, launched at MIT in the fall of 2025.

Shannon Knight, a doctoral candidate at the Massachusetts Institute of Technology, is developing a CRISPR-based gene therapy targeting SYNGAP1 haploinsufficiency, MIT reported. The rare neurodevelopmental disorder causes childhood-onset epilepsy alongside intellectual disabilities and motor challenges.

The condition occurs when a mutation leaves one of the two copies of the SYNGAP1 gene nonfunctional. The gene regulates brain development and communication between neurons. Symptoms typically emerge in children as young as 4 months old, including movement difficulties, disrupted sleep, and seizures that often become resistant to anti-seizure medications over time. The disorder affects between one and four of every 10,000 children.

Knight conducts her doctoral research in the laboratory of Guoping Feng at MIT's McGovern Institute for Brain Research. Her therapeutic approach uses the CRISPR gene-editing tool to address the genetic cause of the disease rather than relying on symptom management. Early testing in mouse models carrying the disorder alleviated seizures and behavioral phenotypes. The project receives backing from the Rare Brain Disorders Nexus, an MIT initiative established in the fall of 2025.

Feng's laboratory plans to guide the SYNGAP1 therapy toward U.S. Food and Drug Administration approval and clinical trials. The project builds on the lab's earlier CRISPR research for Phelan-McDermid syndrome, another rare chromosome disorder whose corresponding therapy has advanced into patient clinical trials. Knight previously studied cricket auditory neuron regeneration at Bowdoin College and worked on CRISPR in fruit fly models at Harvard University's Perrimon Lab before joining MIT.

Alongside her research, Knight served as a teaching assistant for MIT's experimental molecular neurobiology course and received the institute's Goodwin Medal in 2025. After finishing her doctorate, Knight plans to conduct postdoctoral research before seeking a faculty position at a liberal arts college.

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