Fig. 1

Mechanisms of gene-specific therapies against neurological diseases used in clinical practise and tested in clinical trials. Gene-specific therapy with ASOs (A, B), small molecules (C), siRNA (D) or viral gene transfer (E, F). (A) Binding of the ASO to the target mRNA leads to RNase H-mediated degradation of the target mRNA. (B) ASO targeting the splice site of a specific exon to mediate exon skipping (1) or exon inclusion (2). Consequently, an isoform of the target protein is expressed. (C) Small molecule targeting the splice site of the exon to mediate exon skipping (1) or exon inclusion (2). Accordingly, an isoform of the target protein is expressed. (D) The target mRNA is degraded after binding to the complementary siRNA that is part of the RISC complex. (E) Viral delivery of exogenous DNA, which codes for the mRNA of choice (gene reconstitution). (F) Virally introduced exogenous DNA, which encodes a miRNA or shRNA that mediates the degradation of the target mRNA