Therapeutic modulation of miR expression and miR carriers. Tumor suppressive miRs can be replenished by miR mimics (a), thereby suppressing translation of mRNAs encoding for oncogenes. On the other hand, oncogenic miRs can be inhibited by ASOs (b), miR-sponges (c), artificial ribonucleases (d), small molecules (e), or the CRISPR/Cas9 system (f). Small molecules have been shown to either suppress oncomiRs or globally enhance miR expression. To increase oligonucleotide stability, chemical modifications can be inserted. Several delivery systems have been established to further increase the stability of the miR therapeutic agent and improve tumor cell targeting, e.g., cationic dendrimers (g), lipoplexes (h), nanoparticles with tumor-specific ligands (i), inorganic nanoparticles (j), micelles (k), polymer nanoparticles (l), and exosomes/microvesicles (m). See text for more details. AGO, argonaute protein; ASOs, antisense-oligonucleotides; AuNPs, gold nanoparticles; DOPC, 1,2 dioleoyl-sn glycerol-3 phosphatidylcholine-lipid nanoparticles; EDVs, EnGeneIC Delivery Vehicle; LNA, locked nucleic acid; NLE, neutral lipid emulsions; PAMAM, poly(amidoamine); PEI, poly(ethyleneimine); pHLIP, pH low insertion peptide; PLGA, Poly(lactide-co-glycolide); Pol II, RNA-polymerase II; PPI, poly(propylenimine); RISC, RNA-induced silencing complex.