Genetic Medicine Advances: Dravet Gene Editing, Prenatal Hemophilia Therapy, and Valproate Risk Test

Three recent studies describe progress in genetic medicine: a prenatal cell and gene therapy for hemophilia A showed no maternal exposure in sheep, adenine base editing corrected a mutation causing Dravet syndrome in mice, and researchers moved toward a genetic test for valproic acid safety in pregnancy.

In a study published in Science Translational Medicine, gene editing repaired a disease-causing DNA error in mice with Dravet syndrome, a rare, incurable, and potentially deadly form of childhood epilepsy. After the edit, treated mice had far fewer seizures and lived much longer, suggesting a one-time genetic correction could treat the root cause of the disease rather than manage symptoms. The work focused on a specific Dravet-causing SCN1A variant called R613X, which prevents cells from producing a full, functional Nav1.1 channel. Researchers used adenine base editing, a precision approach that rewrites a single DNA letter without cutting both strands, delivered via a single injection into the brain of very young mice on day one or day 12 after birth. In treated mice, the team corrected nearly 60% of the mutated DNA, and almost all gene expression appeared normal. Mice treated at birth had a significant survival improvement, while those treated on day 12 also benefited, with lasting protection into young adulthood and very low levels of unintended DNA changes.

The study follows the Food and Drug Administration's February 2026 issuance of its Plausible Mechanism Framework guidance, which outlines a regulatory pathway for individualized therapies targeting specific genetic conditions. Dravet syndrome, which begins in infancy or early childhood, is characterized by drug-resistant epilepsy, spontaneous and fever-triggered seizures, developmental impairments, and a high risk of sudden unexpected death. An estimated 15,000–20,000 patients live with it in the United States. The research was co-led by a senior study director at The Jackson Laboratory's Rare Disease Translational Center, building on a collaboration between the center's vice president and a core member of the Broad Institute, along with a pediatric neurologist at Children's Hospital of Philadelphia.

Separately, an experimental prenatal cell and gene therapy for hemophilia A called PLC-mcoET3 showed maternal safety in a study in sheep published in Prenatal Diagnosis. The therapy uses human placental cells engineered to produce mcoET3, a modified form of factor VIII, and is designed to restore clotting protein production before birth. The engineered cells were injected into the fetus's abdominal cavity at 59–65 gestation days in sheep, roughly equivalent to 16–18 gestational weeks in humans. Researchers found no detectable exposure of the pregnant sheep to the transplanted cells, the mcoET3 genetic material, or the FVIII protein, and no evidence of immune responses against the transplanted cells or the clotting protein. Blood samples collected during pregnancy and up to two years after birth showed no antibodies against the transplanted cells. Previous studies by the same team found the prenatal treatment produced clinically meaningful and long-lasting FVIII activity persisting for more than three years while reducing bleeding complications, without evidence of toxicity or immune responses against FVIII.

Researchers at Monash University, alongside Australian and international collaborators and the Raoul Wallenberg Australian Pregnancy Register, identified a type of DNA sequence variation in mothers that can modify the risk of their child being harmed if they take valproic acid during pregnancy. The study, published in Neurology, found that valproic acid affects the function of molecules that bind to DNA and regulate gene activity during fetal development, and that maternal genetic variants can affect this binding. Around 10% of babies born to mothers who take valproic acid during pregnancy have a structural birth defect, ranging from severe neural tube defects to milder defects such as cleft palate. The team is developing a genetic test to identify who could safely take the medication, because for some women valproate is the only medication that controls their seizures. A separate study by the same group, published in Neurology in November, used deep learning models to integrate genomic and clinical data to predict response to first-line treatments in people with newly diagnosed epilepsy. The next phase will use deep learning tools to predict the effects of genetic variants on drug therapy and adverse effects, enabled by the University's MAVERIC supercomputer.