Other RNA transcripts with partial complementarity

Other RNA transcripts with partial complementarity is a descriptive term used to identify endogenous RNA molecules that are unintentionally targeted by sequence-based therapeutics like siRNAs or ASOs. These transcripts possess sequences that are not perfectly matched to the drug but share enough homology—particularly in the 6-8 nucleotide 'seed region'—to allow for hybridization and subsequent biological activity [Jackson et al., 2003]. This interaction typically occurs in the 3' untranslated regions (UTRs) of messenger RNAs, leading to their degradation or the inhibition of their translation into proteins [Birmingham et al., 2006]. While these transcripts are not the intended therapeutic targets, they are a major focus in drug design because their suppression can lead to significant off-target toxicity and side effects [Soutschek et al., 2004]. Computational algorithms and experimental methods like RNA-seq are routinely employed to predict and monitor the impact of drugs on these transcripts to ensure safety [Fedorov et al., 2006]. Consequently, this category represents a critical safety parameter rather than a traditional pharmacological target.

Other names

Off-target RNA transcriptsSeed-matched transcriptsNon-target mRNAs with partial homologyOff-target RNAs

Unintended sequence-specific hybridization leading to RNA-induced silencing complex (RISC)-mediated degradation or translational repression of non-target transcripts [Jackson et al., 2003; Birmingham et al., 2006].