LAUSR

Significance The ability to repair mutations in situ is a large unmet need for neurological disorders, such as Rett syndrome, a disorder due to sporadic mutations in the gene encoding Methyl CpG binding protein 2 (MECP2). In this study, we find that a targeted RNA-editing approach effectively repairs a patient mutation by restoring wild-type MeCP2 protein expression and function in the mouse model. As a result, longevity is greatly improved and respiratory dysfunction, a hallmark phenotype among patients, is rescued to wild-type levels. This study represents a proof-of-concept for use of in vivo targeted RNA editing to attenuate disease phenotypes in mouse models for human neurological disorders.