Non-microRNA-21 RNAs with partial sequence complementarity

Non-microRNA-21 RNAs with partial sequence complementarity refer to a diverse group of endogenous RNA transcripts that share sequence homology with microRNA-21 (miR-21), a potent oncomir and driver of fibrosis (Thum et al., Nature, 2008). These molecules are not therapeutic targets themselves but represent a significant class of off-targets for drugs designed to inhibit miR-21, such as antisense oligonucleotides (ASOs) like Lademirsen (RG-012) (Regulus Therapeutics, 2023). The primary concern involves the seed region of the ASO, which can hybridize with partially complementary sequences in the 3' untranslated regions (UTRs) of unintended messenger RNAs (mRNAs), leading to their degradation or translational repression (Jackson et al., Nature Biotechnology, 2003). This off-target binding can result in unintended biological effects and toxicity, complicating the safety profile of miR-21-targeted therapies. In clinical development, these RNAs are scrutinized to ensure that the therapeutic agent maintains high specificity for miR-21 over other cellular RNAs (Burchard et al., Nature Biotechnology, 2009). Consequently, they are a major focus of bioinformatic screening and lead optimization in the field of RNA therapeutics. Understanding the landscape of these partially complementary RNAs is essential for minimizing adverse events in patients treated for conditions like Alport syndrome or solid tumors.

Other names

Off-target transcriptsmiR-21-homologous RNAsSeed-matched off-targets

Unintended hybridization and subsequent silencing of non-target transcripts by antisense oligonucleotides designed for miR-21 (Jackson et al., Nature Biotechnology, 2003).