Figure 1.

Conceptual scheme illustrating the features and functionalities of regulatory ncRNAs as well as opportunities and challenges they bring to clinics. (A) Functionalities of ncRNAs enable them with clinical potential and bring novel opportunities to clinics. Regulatory ncRNAs can function in chromatin remodeling, post-transcriptional regulation and transcriptional regulation. Based on these functionalities, experimental tools such as the CRISPR technique has been established to avail both research and clinics; besides, ncRNAs can capture dynamic subtle cellular changes pathological stimuli that are difficult to be precisely monitored using DNAs or proteins, and targeting miRNAs can effectively regulate many downstream target genes which is difficult to achieve using conventional strategies. (B) Several features of ncRNAs make clinical translation of ncRNAs challenging. NcRNAs are featured by promoting disease in one tissue but being protective in another, therefore, enabling tissue-specific drug delivery is of crucial importance when targeting ncRNAs in clinics. NcRNAs may be subjected to chronic loss-of-function adaptation, leading to inconsistencies observed between short-term inhibition and genetic deletion in some cases, and how to prevent drug efficacy decline with time imposes another big challenge. LncRNAs take advantages of both sequence matching and secondary and/or tertiary structures to take actions, and miRNAs can regulate multiple targets simultaneously, rendering it more important and complicated to prevent off-target effect. Oligonucleotide sequence may be toxic, which makes the safety issue more significant on drug delivery.