Drug target miRNAs: Chances and challenges

Trends in Biotechnology

Volumn 32, Issue 11, 2014, Pages 578-585

  Schmidt, Marco F ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Antisense agents; Drug discovery; MiRNA; MiRNA induced silencing complex; RNAi; Small molecule miRNA modulators

Indexed keywords

GENES;

ANTISENSE AGENT; DRUG DISCOVERY; MIRNA; MIRNA-INDUCED SILENCING COMPLEX; RNAI; SMALL MOLECULES;

RNA;

AMINOGLYCOSIDE ANTIBIOTIC AGENT; ANTISENSE OLIGONUCLEOTIDE; ARGONAUTE 2 PROTEIN; ENOXACIN; ERLOTINIB; MICRORNA; MICRORNA 122; MICRORNA 21; MICRORNA 34A; MIRAVIRSEN; MRX34; SHORT HAIRPIN RNA; SMALL INTERFERING RNA; UNCLASSIFIED DRUG;

CRYSTAL STRUCTURE; DOWN REGULATION; DRUG TARGETING; GENE SILENCING; HUMAN; LIGAND BINDING; MOLECULAR WEIGHT; NUCLEOTIDE SEQUENCE; POST TRANSCRIPTIONAL GENE REGULATOR; REGULATOR GENE; REVIEW; RNA PROCESSING; UPREGULATION; ANTAGONISTS AND INHIBITORS; DRUG DEVELOPMENT; DRUG EFFECTS; GENE EXPRESSION REGULATION; METABOLISM; PHARMACOLOGY; PROCEDURES; TRENDS;

DRUG DISCOVERY; GENE EXPRESSION REGULATION; HUMANS; MICRORNAS; PHARMACOLOGY;

EID: 84908221196     PISSN: 01677799     EISSN: 18793096     Source Type: Journal    
DOI: 10.1016/j.tibtech.2014.09.002     Document Type: Review

References (43)

1. Drews J., Ryser S. The role of innovation in drug development. Nat. Biotechnol. 1997, 15:1318-1319.
2. Overington J.P., et al. How many drug targets are there?. Nat. Rev. Drug Discov. 2006, 5:993-996.
3. Hopkins A.L., Groom C.R. The druggable genome. Nat. Rev. Drug Discov. 2002, 1:727-730.
4. Dykxhoorn D.M., et al. Killing the messenger: short RNAs that silence gene expression. Nat. Rev. Mol. Cell Biol. 2003, 4:457-467.
5. Fabian M.R., Sonenberg N. The mechanism of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat. Struct. Mol. Biol. 2012, 19:586-593.
6. Kole R., et al. RNA therapeutics: beyond RNA interference and antisense oligonucleotides. Nat. Rev. Drug Discov. 2012, 11:125-140.
7. Bader A.G. miR-34 - a microRNA replacement therapy is headed to the clinic. Front. Genet. 2012, 3:120.
8. Zhao J., et al. In-depth analysis shows synergy between erlotinib and miR-34a. PLoS ONE 2013, 9:e89105.
9. Kim D-H., et al. Synthetic dsRNA substrates enhance RNAi potency and efficacy. Nat. Biotechnol. 2005, 23:222-226.
10. Krützfeldt J., et al. Silencing of microRNAs in vivo with antagomirs. Nature 2005, 438:685-689.
11. Koshkin A.A., et al. LNA (locked nucleic acid): synthesis of the adenine, cytosine, guanine, 5-methyl cytosine, thymine, and uracil nicyclonucleoside monomers, oligomers, and unprecedented nucleic acid recognition. Tetrahedron 1998, 54:3607-3630.
12. Janssen H.L., et al. Treatment of HCV infection by targeting microRNA. N. Engl. J. Med. 2013, 368:1685-1694.
13. Jopling C.L., et al. Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science 2005, 309:1577-1581.
14. Lanford R.E., et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 2010, 327:198-201.
15. Machlin E.S., et al. Masking the 5' terminal nucleotides of the hepatitis C virus genome by an unconventional microRNA-target RNA complex. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:3193-3198.
16. Shimakami T.D., et al. Base pairing between hepatitis C virus RNA and microRNA 122 3' of its seed sequence is essential for genome stabilization and production of infectious virus. J. Virol. 2012, 86:7372-7383.
17. Lindow M., Kauppinen S. Discovering the first microRNA-targeted drug. J. Cell Biol. 2012, 199:407-412.
18. Gumireddy K., et al. Small-molecule inhibitors of microRNA miR-21 function. Angew. Chem. Int. Ed. Engl. 2008, 47:7482-7484.
19. Young D.D., et al. Small molecule modifiers of microRNA miR-122 function for the treatment of hepatitis C virus infection and hepatocellular carcinoma. J. Am. Chem. Soc. 2010, 132:7976-7981.
20. Shan G., et al. A small molecule enhances RNA interference and promotes microRNA processing. Nat. Biotechnol. 2010, 26:933-940.
21. Lu J., et al. MicroRNA expression profiles classify human cancers. Nature 2005, 435:834-838.
22. Melo S., et al. Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:4394-4399.
23. Nahar S., et al. Anticancer therapeutic potential of quinazoline based small molecules via upregulation of miRNAs. Chem. Commun. (Camb.) 2014, 50:4639-4642.
24. Davies B.P., Arenz C. A homogenous assay for microRNA maturation. Angew. Chem. Int. Ed. Engl. 2006, 45:5550-5552.
25. Bose D., et al. The tuberculosis drug streptomycin as a potential cancer therapeutic: inhibition of miR-21 function by directly targeting its precursor. Angew. Chem. Int. Ed. Engl. 2012, 51:1019-1023.
26. Velagapudi S.P., et al. Sequence-based design of bioactive small molecules that target precursor microRNAs. Nat. Chem. Biol. 2014, 10:291-297.
27. Bose D., et al. A molecular-beacon screen for small molecule inhibitors of miRNA maturation. ACS Chem. Biol. 2013, 8:930-938.
28. Neubacher S., et al. A rapid assay for miRNA maturation by using unmodified pre-miRNA. ChemBioChem 2011, 12:2302-2305.
29. Schirle N.T., MacRae I.J. The crystal structure of human Argonaute 2. Science 2012, 336:1037-1040.
30. Elkayam E., et al. The structure of human Argonaute-2 in complex with miR20a. Cell 2012, 150:100-110.
31. Tan G.S., et al. Small molecule inhibition of RISC loading. ACS Chem. Biol. 2012, 7:403-410.
32. Masciarelli S., et al. A small-molecule targeting the microRNA binding domain of Argonaute 2 improves the retinoic acid differentiation response of the acute promyelocytic leukemia cell line NB4. ACS Chem. Biol. 2014, 9:1674-1679.
33. Wang Y., et al. Nucleation, propagation, and cleavage of target RNAs in Ago silencing complexes. Nature 2009, 461:754-761.
34. Bartel D.P. MicroRNAs: target recognition and regulatory functions. Cell 2009, 136:215-233.
35. Chi S.W., et al. An alternative mode of microRNA target recognition. Nat. Struct. Mol. Biol. 2012, 19:321-327.
36. Kumar S., et al. Understanding the effect of LNA and 2'-O methyl modification on the hybridization thermodynamics of miRNA-mRNA pair in the presence and absence of AfPiwi protein. Biochemistry 2014, 53:1607-1615.
37. Obad S., et al. Silencing of microRNA families by seed-targeting tiny LNAs. Nat. Genet. 2011, 43:371-378.
38. Schmidt M.F., et al. MicroRNA-specific Argonaute 2 protein inhibitors. ACS Chem. Biol. 2013, 8:2122-2126.
39. Matsuyama Y., et al. Functional regulation of RNA-induced silencing complex by photoreactive oligonucleotides. Bioorg. Med. Chem. 2013, 22:1003-1007.
40. Schmidt M.F., Rademann J. Dynamic template-assisted strategies in fragment-based drug discovery. Trends Biotechnol. 2009, 27:512-521.
41. Schmidt M.F., et al. Sensitized detection of inhibitory fragments and iterative development of non-peptidic protease inhibitors by dynamic ligation screening. Angew. Chem. Int. Ed. Engl. 2008, 47:3275-3278.
42. Schmidt M.F., et al. Selective identification of cooperatively binding fragments in a high-throughput ligation assay enables development of a picomolar caspase-3 inhibitor. Angew. Chem. Int. Ed. Engl. 2009, 48:6346-6349.
43. Schmidt M.F., et al. Dynamic substrate enhancement for the identification of specific, second-site-binding fragments targeting a set of protein tyrosine phosphatases. ChemBioChem 2011, 12:2640-2646.