New ‘proof of principle’ research from the lab of Gail Mandel has demonstrated for the first time that in vivo programmable RNA editing can be used to repair mutations in mouse models of neurological disease. In the study published July 14 in the journal Cell Reports, first author John Sinnamon and collaborators introduced adeno-associated virus bearing Mecp2 guide-targeted editing enzyme or ‘editase’ into the hippocampus of a Rett syndrome mouse model. Research from the team showed that the ‘editase’ repaired approximately half of the mutant Mecp2 RNA and restored MeCP2 protein function across multiple neuronal populations.
Rett syndrome is a neurodevelopmental disorder that is caused by mutations in the gene encoding the X-linked transcription factor methyl CpG binding protein 2, or MECP2, which is critical for normal brain function. Mutations that cause Rett syndrome result in reductions in MeCP2 levels and/or disrupt MeCP2 function.
This is the group’s second success using the site-directed RNA approach and builds on research from 2017 when they successfully repaired mutant Mecp2 mRNA and restored MeCP2 protein function in cultured neurons from a Rett mouse model.