Antisense oligonucleotide therapy in a humanized mouse model of <i>MECP2</i> duplication syndrome.

ABSTRACT: Many intellectual disability disorders are due to copy number variations, and, to date, there have been no treatment options tested for this class of diseases. MECP2 duplication syndrome (MDS) is one of the most common genomic rearrangements in males and results from duplications spanning the methyl-CpG binding protein 2 (MECP2) gene locus. We previously showed that antisense oligonucleotide (ASO) therapy can reduce MeCP2 protein amount in an MDS mouse model and reverse its disease features. This MDS mouse model, however, carried one transgenic human allele and one mouse allele, with the latter being protected from human-specific MECP2-ASO targeting. Because MeCP2 is a dosage-sensitive protein, the ASO must be titrated such that the amount of MeCP2 is not reduced too f

SUBMITTER: Shao Y 

PROVIDER: S-EPMC8976688 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature