Base editing repairs Dravet mutation in mice

Researchers at the Broad Institute, The Jackson Laboratory and Children’s Hospital of Philadelphia reported on May 13 that a base-editing treatment corrected a disease-causing Dravet syndrome mutation in mice and reduced seizures while extending survival. The study, published in *Science Translational Medicine*, used an adenine base editor to repair a recurrent SCN1A mutation linked to the severe childhood epilepsy disorder. In treated neonatal mice, the authors reported 90% survival at 45 days versus 27% in vehicle-treated controls. The work remains preclinical, but the authors said it shows that direct correction of a pathogenic brain mutation is possible in a living animal. ### Which mutation did the researchers go after? The paper identified the target as SCN1A R613X, a recurrent loss-of-function variant found in some patients with Dravet syndrome. Dravet syndrome is a developmental and epileptic encephalopathy that begins in infancy, and more than 90% of diagnosed patients have an SCN1A mutation, according to the Dravet Syndrome Foundation. PubMed’s abstract said the disease is marked by drug-resistant epilepsy, temperature-sensitive seizures, cognitive impairment and a high incidence of sudden unexpected death in epilepsy. (pubmed.ncbi.nlm.nih.gov) The authors wrote that current approved treatments manage symptoms but do not correct the root cause of the disease. ### How was the edit delivered into the mouse brain? The researchers used a dual AAV9, or adeno-associated virus serotype 9, system to deliver an optimized adenine base editor into Scn1aR613X/+ mice. (pubmed.ncbi.nlm.nih.gov) The base editor was given through a single injection into the brain of very young mice, according to the Jackson Laboratory release and EurekAlert summary of the study. The Science paper reported 72% correction efficiency in engineered human embryonic kidney 293T cells and 92% in mouse Neuro-2a cells before the team moved into the animal model. (pubmed.ncbi.nlm.nih.gov) In neonatal mice, the treatment produced 59% DNA editing and 97% mRNA editing in bulk neocortices, the abstract said. ### What changed in the treated mice? The authors reported that AAV9-ABE treatment restored parvalbumin-expressing inhibitory neuron excitability and sodium current to wild-type levels. (pubmed.ncbi.nlm.nih.gov) They also said the intervention reduced both spontaneous seizures and heat-triggered seizures in the mouse model. The clearest survival result came in mice treated as neonates: 90% of treated animals were alive at 45 days, compared with 27% of vehicle-treated mice, which the paper described as a 3.3-fold improvement. (pubmed.ncbi.nlm.nih.gov) In mice treated later, at 12 days old, 82% survived to 60 days versus 27% of controls, a 3.0-fold improvement, according to the paper. ### Who led the work, and what did they say? PubMed listed Andrew T. Nelson, Sophie F. (pubmed.ncbi.nlm.nih.gov) Hill and Matthew Simon among the lead authors, with Cathleen M. Lutz, Ethan M. Goldberg and David R. Liu as senior authors. Their affiliations included the Broad Institute, Harvard University, The Jackson Laboratory, UMass Chan Medical School and the University of Pennsylvania system. Matthew Simon, a senior study director at The Jackson Laboratory’s Rare Disease Translational Center who co-led the study, said in a Jackson Laboratory release that the results provide “proof of concept” for a genetic correction approach in Dravet syndrome. (pubmed.ncbi.nlm.nih.gov) The same release said the work built on a collaboration involving Lutz, Broad’s David Liu and CHOP pediatric neurologist Ethan Goldberg. ### How does this fit into the broader Dravet treatment race? The study enters a field already pursuing several genetic strategies for SCN1A-related epilepsies, including gene therapy and RNA-based approaches. A separate *Science Translational Medicine* paper published the same day reported prime editing of a pathogenic Scn1a allele in a GEFS+ mouse model, another SCN1A-linked epilepsy, showing that multiple precision-editing approaches are being tested in related disorders. (broadinstitute.org) The Broad Institute release also pointed to a shifting regulatory backdrop. In February 2026, the U.S. Food and Drug Administration issued guidance on its Plausible Mechanism Framework for individualized therapies targeting specific genetic conditions, according to the release and EurekAlert summary. May 13 is the next concrete milestone in this line of work because that is when *Science Translational Medicine* published the full paper, DOI 10.1126/scitranslmed.adx5999, with the survival curves, editing data and methods. (science.org) The named participants in the next step are the same academic groups at Broad, Jackson Laboratory and Children’s Hospital of Philadelphia, which described the findings as preclinical and did not announce a human trial in the paper or accompanying releases. (pubmed.ncbi.nlm.nih.gov) (broadinstitute.org)