Other cellular RNAs with partial complementarity to the anti-miR-128-1 sequence

Other cellular RNAs with partial complementarity to the anti-miR-128-1 sequence refer to a diverse set of transcripts, including messenger RNAs (mRNAs) and non-coding RNAs, that may unintentionally bind to antisense oligonucleotides (ASOs) designed to inhibit microRNA-128-1. miR-128-1 is a critical regulator of neuronal signaling and is frequently investigated as a therapeutic target for epilepsy and malignant glioma (PMID: 23467082). The interaction between an anti-miR and these other RNAs occurs due to sequence homology, where the ASO recognizes similar seed regions or partial sequences in non-target transcripts (PMID: 24837728). Such off-target binding can lead to the unintended degradation of these RNAs via RNase H-mediated cleavage or the blocking of their biological function through steric hindrance (PMID: 30135580). These interactions are a primary source of sequence-specific toxicity in oligonucleotide therapeutics and can result in adverse cellular responses or systemic side effects. Consequently, these RNAs are not therapeutic targets but are instead considered safety liabilities that must be rigorously screened during the lead optimization of anti-miR-128-1 candidates (PMID: 25437558). Understanding the landscape of these off-targets is essential for ensuring the precision and safety of microRNA-based interventions.

Other names

Off-target RNAs of anti-miR-128-1Non-target transcripts with sequence homology to miR-128-1ASO off-targetsUnintended RNA binding partners

Sequence-specific hybridization leading to unintended degradation or translational inhibition of non-target transcripts.