Fig. 2.

a siRNA results in a knockdown of gene expression. The double-stranded precursor of the siRNA molecule is brought into the cell and subsequently cleaved by the DICER protein. The resulting single-stranded siRNA molecule binds to the Argonaut (AGO) protein and interacts with the RNA-induced silencing complex (RISC), directing the siRNA to the corresponding mRNA sequence and resulting in a knock-down of protein expression, either by cleavage, degradation or translation repression [44, 45]. b ASOs are short single-stranded RNA sequences, structurally stabilized through chemical modifications, that can lead to the knock-down of a corresponding mRNA molecule by steric block, splice modulation, or RNAse H-mediated cleavage of the mRNA [44]. c Small interfering RNA (siRNA) and antisense oligonucleotides (ASOs) can knock down gene expression. Modifications in the backbone (phosphorothioate linkage and incorporation of fluor-, amine-, halogen-, deoxy- or methyl-groups) can be used in both the siRNA precursor as well as in the single-stranded antisense oligonucleotides to increase stability. Locked nucleic acids also prevent the degradation of the single-stranded RNA molecules [46]. 2′-O-methoxyethyl (-MOE), 2′-O-methyl (-O-Me), 2’-Fluoro (-F), phosphorodiamidate morpholino oligomers (PMOs), locked nucleic acids (LNAs)