AAV.CAP-B10-DIMMER-KCNQ2

AAV.CAP-B10-DIMMER-KCNQ2 is an experimental adeno-associated virus (AAV) gene therapy designed for the treatment of KCNQ2 developmental and epileptic encephalopathy (KCNQ2-DEE). Developed by researchers at the California Institute of Technology, the therapy utilizes the neuronal-tropic AAV.CAP-B10 capsid to deliver a wild-type KCNQ2 transgene. A key feature of this construct is the inclusion of a Dosage-Invariant miRNA-Mediated Expression Regulator (DIMMER) circuit, which employs a synthetic miRNA-based incoherent feed-forward loop to achieve uniform, tunable neuronal expression of KCNQ2 independent of the viral dose at the single-cell level. This precision control is intended to address the narrow therapeutic window of KCNQ2, where both loss- and gain-of-function mutations cause disease. In preclinical mouse models (KCNQ2-T274M), the therapy has shown potential in reducing seizure susceptibility and normalizing cognitive performance.