The versatility of oligonucleotides as potential therapeutics.

Eckstein, Fritz

Oligonucleotides can in a variety of ways inhibit gene expression by interfering with translation. Oligonucleotides that are complementary to a target mRNA, antisense oligonucleotides, can prevent translation either by cleaving the target or by physically blocking the process. Additionally, oligonucleotides can correct the undesired splicing of pre-mRNA. RNA interference using double-stranded oligoribonucleotides also results in cleavage of the target mRNA. Catalytically competent ribozymes and DNAzymes can have the same effect. Even with no RNA as target, oligonucleotides can be selected as aptamers to bind to any protein to inhibit its activity. Moreover, oligonucleotides can act as decoys particularly for transcription factors to prevent binding to the promoter. A different mode of action is the activation of Toll-like receptors to induce an immune response. Several pathways for drug development are still in their infancy, for example microRNAs and antagomirs.