A UC San Diego-led team reported individualized antisense oligonucleotide (ASO) designs that reduced seizures in two boys with rare SCN2A-related developmental and epileptic encephalopathies and enabled one patient to walk independently. The findings were published in Nature Medicine. The study used patient-specific variants in SCN2A—gain-of-function or mixed loss/gain-of-function—to tailor ASOs intended to knock down pathogenic signaling. Researchers noted the approach is particularly suited for disorders driven by a single causal variant and may not fully address polygenic disease features. Ionis Pharmaceuticals supported the ASO design and testing used in the study. While only early clinical evidence, the results add to growing proof that precision ASO engineering can translate variant biology into clinically meaningful outcomes in ultra-rare neurologic disease.