Figure 3.

Therapeutic Approaches to Rescue miRNA Dysfunction

Exosome/liposome, viral vectors (lentivirus [LV], adeno-associated virus [AAV], adeno, and plasmid), nanoparticles/polymers, aptamer-mediated antagomiR, and miRNA mimic delivery into the pulmonary cells. (A) Small molecules bind to Drosha and Dicer processing sites of human miRNAs that are disease associated and inhibit their biogenesis. (B) miRNA mimics function like endogenous miRNAs restoring the activity of a miRNA. (C and D) Binding of single-stranded antagomiRs having complementary sequences to the target endogenous miRNA genome sequence and inhibiting the synthesis of disease-causing miRNAs (C), and antagomiRs having seed sequence sequesters the endogenous free miRNA target inhibiting the activity (D). AGO, Argonaute proteins; DGCR8, DiGeorge syndrome critical region gene 8; m7G cap, 7-methylguanosine; miRISC, miRNA-induced silencing complex; miRNA, microRNA; pre-miRNA, miRNA precursor; pri-miRNA, primary miRNA; RAN-GTP, Ras-related nuclear protein coupled with guanosine-5′-triphosphate; T, inhibitory effect; TRBP, transactivating response RNA-binding protein.