Complementary target RNA sequence

A complementary target RNA sequence is a specific nucleotide sequence within a ribonucleic acid molecule—typically messenger RNA (mRNA) or pre-mRNA—that serves as the binding site for therapeutic oligonucleotides. This targeting mechanism relies on Watson-Crick base pairing between the drug (such as an antisense oligonucleotide or siRNA) and the endogenous RNA strand (Bennett & Swayze, 2010, Annual Review of Pharmacology and Toxicology). By binding to these sequences, therapeutics can trigger various biological outcomes, including RNase H-mediated degradation of the mRNA, physical blockade of the translation machinery, or modulation of alternative splicing (Watts & Corey, 2012, Journal of Pathology). This approach allows for the highly specific targeting of disease-causing proteins that may be undruggable by traditional small molecules, particularly those involved in rare genetic diseases and certain cancers. RNA targeting is a cornerstone of precision medicine, enabling the down-regulation of toxic proteins or the restoration of functional protein expression. Clinical examples include the targeting of the SMN2 pre-mRNA sequence to treat spinal muscular atrophy and the TTR mRNA sequence to treat hereditary transthyretin-mediated amyloidosis (Crooke et al., 2021, Nature Reviews Drug Discovery).

Other names

RNA targetTargeted RNA sequenceAntisense target sequenceOligonucleotide target site

Watson-Crick base pairing leading to RNase H-mediated cleavage, RNA interference (RNAi), or steric hindrance of splicing/translation (Crooke et al., 2021, Nature Reviews Drug Discovery).