In Vivo Repair of a Protein Underlying a Neurological Disorder by Programmable RNA Editing

著者: John R. Sinnamon, Susan Y. Kim, Jenna R. Fisk, Zhen Song, Hiroyuki Nakai, Sophia Jeng, Shannon K. McWeeney, Gail Mandel - Cell Reports 2020 被引用: 64

mice with an adeno-associated virus expressing the hyperactive catalytic domain of adenosine deaminase acting on RNA 2 and Mecp2 guide. After 1 month, 50% of Mecp2 RNA is recoded in three different hippocampal neuronal populations. MeCP2 protein localization to heterochromatin is restored in neurons to 50% of wild-type levels. Whole-transcriptome RNA analysis of one neuronal population indicates that the majority of off-target editing sites exhibit rates of 30% or less. This study demonstrates that programmable RNA editing can be utilized to repair mutations in mouse models of neurological disease.