Schematic representation of sbASO-mediated disinhibition approach on MECP2 3′ UTR. (A) RNA-induced silencing complexes (RISCs) bind to complementary microRNA response elements (MREs) on the MECP2 3′ UTR, resulting in translational repression or transcript destabilization. (B) sbASOs are designed to target these MREs, thereby preventing the binding of RISCs. This action blocks miRNA-mediated repression, allowing for increased expression of MeCP2. The schematic illustrates the potential of sbASOs to de-repress MeCP2 by competitively inhibiting miRNA binding to the MECP2 3′ UTR. (C) Sequences of sbASO target sites and percentage conservation between mice and humans are shown. (ORF) Open reading frame.
