Gene editing can repair a DNA error in mice that causes Dravet syndrome, a rare, incurable, and potentially deadly form of childhood epilepsy. After the edit, the mice have far fewer seizures and live much longer.
Published in Science Translational Medicine , the results suggest that a one-time genetic correction could someday treat the root cause of the disease rather than just managing its symptoms. The work represents a major step for genetic medicine, as restoring disease-relevant brain function with gene editing tools remains a major challenge.
The study also reflects growing momentum behind gene editing as a therapeutic platform for rare diseases. In February 2026, the Food and Drug Administration issued its Plausible Mechanism Framework guidance, outlining a regulatory pathway for individualized therapies targeting specific genetic conditions. It recognizes that for rare genetic diseases, a well-characterized biological mechanism can serve as the foundation for approval where large clinical trials are not feasible.
"For families affected by Dravet syndrome, our study provides proof of concept that a genetic correction approach could have real impact, a future with treatments that don't just manage the disease but actually address its cause," said Matthew Simon, a senior study director at The Jackson Laboratory (JAX) Rare Disease Translational Center (RDTC) who co-led the study. "We're at an inflection point in genetic medicine, where we can now actually repair the DNA itself."
The work builds on a long-standing collaboration between JAX's RDTC Vice President Cathleen (Cat) Lutz and David Liu, a core member of the Broad Institute (Broad) and pioneer in gene editing. The team has contributed to the growing momentum behind gene editing as a viable therapeutic strategy for rare diseases, a field that has seen landmark advances including the treatment of Baby KJ Muldoon in 2025. The latest breakthrough comes from their partnership with Ethan M. Goldberg, a pediatric neurologist at Children's Hospital of Philadelphia (CHOP) and director of the Epilepsy Neurogenetics Initiative.
Dravet syndrome is a neurodevelopmental disorder that begins in infancy or early childhood, with symptoms including drug-resistant epilepsy, spontaneous and fever-triggered seizures, and significant developmental impairments. Patients face a high risk of sudden unexpected death. Yet current approved therapies often require repeated dosing or long-term intervention to treat symptoms. While the disease is rare by definition, an estimated 15,000–20,000 patients live with it in the United States today, Lutz said.
A new era of precision genetics
The preclinical study focused on a specific Dravet-causing SCN1A variant called R613X. This mutation prevents cells from producing a full, functional Nav1.1 channel, which regulates neuron excitability. This creates an electrophysiological imbalance in certain brain cells, where neurons don't work properly, making the brain overexcitable and prone to seizures.
The researchers used adenine base editing (ABE), a precision gene editing approach that rewrites a single DNA letter without cutting both DNA strands, which preserves genomic integrity and reduces the risk of unintended edits. To correct the mutation in cells and in a mouse model of Dravet syndrome, the base editor was delivered via a single injection into the brain in very young mice, either on day one or day 12 after birth.
The success of the approach is particularly significant, Lutz said, because it applies base editing to one of the most difficult settings for genetic medicine: a neurological disorder involving specialized inhibitory neurons distributed across the brain.
In treated mice, the team corrected nearly 60% of the mutated DNA. Even with partial correction, almost all the gene's expression appeared normal. That is because cells naturally help destroy defective messages from uncorrected genes.
"The advantage here is that once you correct the gene, the cell's own regulatory systems take over again. You're not managing a disease but restoring the biology that was always meant to be there," Simon said.
As predicted, the edit restored the function of the gene and prevented seizures. Unlike untreated mice, the mice treated at birth had a significant survival improvement. Mice treated on day 12 also benefited, with lasting protection into young adulthood and very low levels of unintended DNA changes or other adverse effects in the brain.
"Most patients aren't diagnosed at birth. They're diagnosed after symptoms begin. So, showing that we can intervene later, at an age closer to real patients, is important," Simon said. "There's been a concern that once the brain develops, it may be too late to fix these problems. Our data suggest that's not the case."
Because Dravet syndrome patients often have their own unique mutations, the next step is figuring out how to tailor the approach across the many different versions of the disease and advancing delivery technologies for the clinic.
A new platform for genetic medicine
Last month, a JAX team led by Lutz in collaboration with the same team from the Broad reported using the same gene editing technology to fix mutations in mice and human patient cells with an extremely rare and life-threatening genetic disease called Zellweger spectrum disorder , which impairs liver function in early childhood. In 2025, that team also fixed mutations in mice causing alternating hemiplegia of childhood , a genetic disorder that causes life-threatening seizures in children. For that, they used an approach called prime editing, which rewrites (inserts, deletes, or replaces) short DNA sections instead of fixing single-letter errors.
"We're following a game plan built on years of work in the field, and this project showed how straightforward the process can be when all the pieces come together: the right model, testing the editing strategy, and connecting that all the way through to disease outcomes," Lutz said. "The long-term vision is to build a platform so robust and adaptable that correcting a new mutation becomes a matter of precision and speed rather than starting from scratch, ultimately expanding the reach of genetic medicine to diseases that today can only be managed."
The team is focused on separating the unchanging components of the platform from those that need to be tailored to each disease—primarily the guide molecule that directs the gene editor to the precise location in the DNA that needs to be corrected. The goal is to establish the platform's overall safety and efficacy so that adapting it to new mutations becomes increasingly practical.
"This study gives us hope that base editing could be an effective approach for durably correcting the underlying cause of Dravet syndrome in patients," said David Liu, who is also a Howard Hughes Medical Institute investigator and a professor at Harvard University. "It is also a compelling example of the benefits of working collaboratively across laboratories and institutions to integrate each other's complementary expertise into the foundation for a future treatment for a devastating rare disease."
This work was supported by the National Institutes of Health (grants MIRA R35GM118062, CEGS RM1HG009490, and R01NS110869); the Broad Institute Chemical Biology and Therapeutics Science program funds; the Howard Hughes Medical Institute; the Dravet Syndrome Foundation Research Grant; the Dravet Syndrome Foundation Postdoctoral Fellowship Grant; and The Brody Family Medical Trust Fund Fellowship in "Incurable Diseases" of The Philadelphia Foundation.
Other authors are Andrew T. Nelson, of the Broad Institute of Harvard and MIT; Sophie F. Hill and Jérôme Clatot of Children's Hospital of Philadelphia; Jun Xie of UMass Chan Medical School; Holt A. Sakai, Alexander A. Sousa, and Meirui An of the Broad Institute of Harvard and MIT; and Guangping Gao of UMass Chan Medical School.
