Rett Syndrome Mouse Model Study Points to RNA Editing Possibilities

For a proof-of-principle paper appearing in PNAS this week, a team from the Oregon Health and Science University, the Oregon National Primate Research Center, and the University of Connecticut Health Center demonstrate the possibility of using targeted RNA editing to repair a Rett syndrome-related MECP2 alteration in a mutant mouse model of the neurological condition. Using a MECP2-expressing adeno-associated virus (AAV), the researchers found that they could target a missense guanosine-to-adenosine point mutation in mice without overexpressing the resulting protein, restoring MeCP2 protein expression and reducing Rett-related symptoms in the animals. "Overall, our study supports the idea that a targeted RNA-editing approach has potential to improve symptoms in [a] mouse model of Rett syndrome, and holds promise for other neurological disease models as well," the authors say, noting that "[w]hile AAV-mediated gene expression can endure for years in nonhuman primates, the need for development of new AAV serotypes, with improved widespread tropisms after systemic or more localized delivery methods into the brain, is still pressing."