Other microRNAs with partial sequence complementarity

Other microRNAs with partial sequence complementarity is a descriptive classification used to identify endogenous microRNA (miRNA) molecules that pose a risk for off-target interactions with RNA-based therapeutics (Setten et al., 2019, PMID: 30735154). These miRNAs share sufficient sequence homology—often limited to a short 2-8 nucleotide seed sequence—with synthetic oligonucleotides like small interfering RNAs (siRNAs) or antisense oligonucleotides (ASOs), leading to unintended binding and biological activity (Jackson et al., 2003, PMID: 12799665). While not therapeutic targets themselves, they are critical anti-targets in drug design; their unintended modulation can result in the silencing of non-target genes, disruption of cellular homeostasis, and potential toxicity (Birmingham et al., 2006, PMID: 16604153). Consequently, the characterization of these partially complementary sequences is a vital component of the safety assessment and specificity profiling for any oligonucleotide drug candidate (Kulkarni et al., 2018, PMID: 29335479). Modern drug discovery workflows utilize sophisticated bioinformatics and transcriptomic assays to screen for and mitigate these off-target liabilities early in development.

Other names

Off-target microRNAsNon-target miRNAsSeed-matched microRNAsPartially complementary RNA sequences

Therapeutic oligonucleotides, such as siRNAs, can interact with these microRNAs through partial sequence complementarity, particularly in the seed region (nucleotides 2-8). This interaction allows the drug to enter the RNA-induced silencing complex (RISC) and inadvertently regulate the expression of non-target mRNAs that are naturally controlled by these microRNAs, or directly interfere with the microRNAs' endogenous functions (Birmingham et al., 2006, PMID: 16604153; Jackson et al., 2003, PMID: 12799665).