Pharmacological inhibition of a microRNA family in nonhuman primates by a seed-targeting 8-mer antimiR

Science Translational Medicine

Volumn 5, Issue 212, 2013, Pages

  Rottiers, Veerle ^a,b   Obad, Susanna ^c   Petri, Andreas ^c,d   McGarrah, Robert ^e,f   Lindholm, Marie W ^c   Black, Joshua C ^a,e   Sinha, Sumita ^e   Goody, Robin J ^g   Lawrence, Matthew S ^g   DeLemos, Andrew S ^e   Hansen, Henrik F ^c   Whittaker, Steve ^g   Henry, Steve ^g   Brookes, Rohn ^g   Najafi Shoushtari, Seyed Hani ^a,b,h   Chung, Raymond T ^e   Whetstine, Johnathan R ^a,e   Gerszten, Robert E ^e   Kauppinen, Sakari ^c,d   Näär, Anders M ^a,b  

^a MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c Santaris Pharma AS   (Denmark)

^d AALBORG UNIVERSITY HOSPITAL   (Denmark)

^e MASSACHUSETTS GENERAL HOSPITAL   (United States)

^f DUKE UNIVERSITY MEDICAL CENTER   (United States)

^g RxGen Inc   (United States)

^h WEILL CORNELL MEDICAL COLLEGE   (Qatar)

Author keywords

[No Author keywords available]

Indexed keywords

8 MER MICRORNA 33A ANTIBODY; 8 MER MICRORNA 33AB ANTIBODY; 8 MER MICRORNA 33B ANTIBODY; ABC TRANSPORTER A1; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LIPID; LOCKED NUCLEIC ACID; MICRORNA; MICRORNA 33A; MICRORNA 33B; RNA ANTIBODY; UNCLASSIFIED DRUG;

ABSENCE OF SIDE EFFECTS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CHLOROCEBUS AETHIOPS; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; FEMALE; GENE CONTROL; GENE TARGETING; HOMEOSTASIS; HUMAN; HUMAN CELL; INSULIN RESISTANCE; LOADING DRUG DOSE; MAMMAL CELL; METABOLIC DISORDER; MOUSE; MULTIGENE FAMILY; NONHUMAN; OBESITY; PLASMA HALF LIFE; PRIORITY JOURNAL; RNA SEQUENCE;

ANIMALS; CHOLESTEROL, HDL; FEMALE; GENE SILENCING; HEP G2 CELLS; HUMANS; MICE; MICE, INBRED C57BL; MICRORNAS; PRIMATES;

EID: 84890387599     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3006840     Document Type: Article

References (34)

1. V. Ambros, The functions of animal microRNAs. Nature 431, 350-355 (2004).
2. D. P. Bartel, MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 116, 281-297 (2004).
3. D. P. Bartel, MicroRNAs: Target recognition and regulatory functions. Cell 136, 215-233 (2009).
4. J. Hertel, M. Lindemeyer, K. Missal, C. Fried, A. Tanzer, C. Flamm, I. L. Hofacker, P. F. Stadler; Students of Bioinformatics Computer Labs 2004 and 2005, The expansion of the metazoan microRNA repertoire. BMC Genomics 7, 25 (2006).
5. B. P. Lewis, C. B. Burge, D. P. Bartel, Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15-20 (2005).
6. J. T. Mendell, E. N. Olson, MicroRNAs in stress signaling and human disease. Cell 148, 1172-1187 (2012).
7. R. E. Lanford, E. S. Hildebrandt-Eriksen, A. Petri, R. Persson, M. Lindow, M. E.Munk, S. Kauppinen, H. Ørum, Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327, 198-201 (2010).
8. H. L. Janssen, H. W. Reesink, E. J. Lawitz, S. Zeuzem,M. Rodriguez-Torres, K. Patel, A. J. van der Meer, A. K. Patick, A. Chen, Y. Zhou, R. Persson, B. D. King, S. Kauppinen, A. A. Levin, M. R. Hodges, Treatment of HCV infection by targeting microRNA. N. Engl. J. Med. 368, 1685-1694 (2013).
9. A. Grimson, K. K. Farh, W. K. Johnston, P. Garrett-Engele, L. P. Lim, D. P. Bartel, MicroRNA targeting specificity in mammals: Determinants beyond seed pairing. Mol. Cell 27, 91-105 (2007).
10. S. Obad, C. O. dos Santos, A. Petri, M. Heidenblad, O. Broom, C. Ruse, C. Fu, M. Lindow, J. Stenvang, E.M. Straarup, H. F. Hansen, T. Koch, D. Pappin, G. J. Hannon, S. Kauppinen, Silencing of microRNA families by seed-targeting tiny LNAs. Nat. Genet. 43, 371-378 (2011).
11. Y. Zhang, A. M. Roccaro, C. Rombaoa, L. Flores, S. Obad, S. M. Fernandes, A. Sacco, Y. Liu, H. Ngo, P. Quang, A. K. Azab, F. Azab, P. Maiso, M. Reagan, J. R. Brown, T. H. Thai, S. Kauppinen, I. M. Ghobrial, LNA-mediated anti-miR-155 silencing in low-grade B-cell lymphomas. Blood 120, 1678-1686 (2012).
12. E. Leucci, A. Zriwil, L. H. Gregersen, K. T. Jensen, S. Obad, C. Bellan, L. Leoncini, S. Kauppinen, A. H. Lund, Inhibition of miR-9 de-represses HuR and DICER1 and impairs Hodgkin lymphoma tumour outgrowth in vivo. Oncogene 31, 5081-5089 (2012).
13. B. C. Bernardo, X. M. Gao, C. E. Winbanks, E. J. Boey, Y. K. Tham, H. Kiriazis, P. Gregorevic, S. Obad, S. Kauppinen, X. J. Du, R. C. Lin, J. R. McMullen, Therapeutic inhibition of the miR-34 family attenuates pathological cardiac remodeling and improves heart function. Proc. Natl. Acad. Sci. U.S.A. 109, 17615-17620 (2012).
14. S. H. Najafi-Shoushtari, F. Kristo, Y. Li, T. Shioda, D. E. Cohen, R. E. Gerszten, A. M. Näär, MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science 328, 1566-1569 (2010).
15. K. J. Rayner, Y. Suárez, A. Dávalos, S. Parathath, M. L. Fitzgerald, N. Tamehiro, E. A. Fisher, K. J. Moore, C. Fernández- Hernando, MiR-33 contributes to the regulation of cholesterol homeostasis. Science 328, 1570-1573 (2010).
16. T. J. Marquart, R. M. Allen, D. S. Ory, A. Baldán, miR-33 links SREBP-2 induction to repression of sterol transporters. Proc. Natl. Acad. Sci. U.S.A. 107, 12228-12232 (2010).
17. T. Horie, K. Ono, M. Horiguchi, H. Nishi, T. Nakamura, K. Nagao, M. Kinoshita, Y. Kuwabara, H. Marusawa, Y. Iwanaga, K. Hasegawa, M. Yokode, T. Kimura, T. Kita, MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo. Proc. Natl. Acad. Sci. U.S.A. 107, 17321-17326 (2010).
18. I. Gerin, L. A. Clerbaux, O. Haumont, N. Lanthier, A. K. Das, C. F. Burant, I. A. Leclercq, O. A. MacDougald, G. T. Bommer, Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation. J. Biol. Chem. 285, 33652-33661 (2010).
19. A. Dávalos, L. Goedeke, P. Smibert, C. M. Ramírez, N. P. Warrier, U. Andreo, D. Cirera-Salinas, K. Rayner, U. Suresh, J. C. Pastor-Pareja, E. Esplugues, E. A. Fisher, L. O. Penalva, K. J. Moore, Y. Suárez, E. C. Lai, C. Fernández-Hernando, miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proc. Natl. Acad. Sci. U.S.A. 108, 9232-9237 (2011).
20. K. J. Rayner, F. J. Sheedy, C. C. Esau, F. N. Hussain, R. E. Temel, S. Parathath, J. M. van Gils, A. J. Rayner, A. N. Chang, Y. Suarez, C. Fernandez-Hernando, E. A. Fisher, K. J. Moore, Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. J. Clin. Invest. 121, 2921-2931 (2011).
21. K. J. Rayner, C. C. Esau, F. N. Hussain, A. L. McDaniel, S. M. Marshall, J. M. van Gils, T. D. Ray, F. J. Sheedy, L. Goedeke, X. Liu, O. G. Khatsenko, V. Kaimal, C. J. Lees, C. Fernandez-Hernando, E. A. Fisher, R. E. Temel, K. J. Moore, Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature 478, 404-407 (2011).
22. A. D. Attie, ABCA1: At the nexus of cholesterol, HDL and atherosclerosis. Trends Biochem. Sci. 32, 172-179 (2007).
23. D. J. Rader, A. R. Tall, The not-so-simple HDL story: Is it time to revise the HDL cholesterol hypothesis? Nat. Med. 18, 1344-1346 (2012).
24. -/-mice. J. Am. Heart Assoc. 1, e003376 (2012).
25. R. M. Allen, T. J. Marquart, C. J. Albert, F. J. Suchy, D. Q. Wang, M. Ananthanarayanan, D. A. Ford, A. Baldan, miR-33 controls the expression of biliary transporters, and mediates statin- and diet-induced hepatotoxicity. EMBO Mol. Med. 4, 882-895 (2012).
26. V. Rottiers, S. H. Najafi-Shoushtari, F. Kristo, S. Gurumurthy, L. Zhong, Y. Li, D. E. Cohen, R. E. Gerszten, N. Bardeesy, R. Mostoslavsky, A. M. Näär, MicroRNAs in metabolism and metabolic diseases. Cold Spring Harb. Symp. Quant. Biol. 76, 225-233 (2011).
27. S. Liddie, R. J. Goody, R. Valles, M. S. Lawrence, Clinical chemistry and hematology values in a Caribbean population of African green monkeys. J. Med. Primatol. 39, 389-398 (2010).
28. R. K. Avramoglu, H. Basciano, K. Adeli, Lipid and lipoprotein dysregulation in insulin resistant states. Clin. Chim. Acta 368, 1-19 (2006).
29. E. M. Straarup, N. Fisker, M. Hedtjärn, M. W. Lindholm, C. Rosenbohm, V. Aarup, H. F. Hansen, H. Ørum, J. B. Hansen, T. Koch, Short locked nucleic acid antisense oligonucleotides potently reduce apolipoprotein B mRNA and serum cholesterol in mice and non-human primates. Nucleic Acids Res. 38, 7100-7111 (2010).
30. J. A. Cann, K. Kavanagh, M. J. Jorgensen, S. Mohanan, T. D. Howard, S. B. Gray, G. A. Hawkins, L. A. Fairbanks, J. D. Wagner, Clinicopathologic characterization of naturally occurring diabetes mellitus in vervet monkeys. Vet. Pathol. 47, 713-718 (2010).
31. G. Chen, G. Liang, J. Ou, J. L. Goldstein, M. S. Brown, Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver. Proc. Natl. Acad. Sci. U.S.A. 101, 11245-11250 (2004).
32. -/- mice - Brief report. Arterioscler. Thromb. Vasc. Biol. 33, 1973-1977 (2013).
33. T. J. Marquart, J. Wu, A. J. Lusis, A. Baldán, Anti-miR-33 therapy does not alter the progression of atherosclerosis in low-density lipoprotein receptor-deficient mice. Arterioscler. Thromb. Vasc. Biol. 33, 455-458 (2013).
34. J. Elmén, M. Lindow, A. Silahtaroglu, M. Bak, M. Christensen, A. Lind-Thomsen, M. Hedtjärn, J. B. Hansen, H. F. Hansen, E. M. Straarup, K. McCullagh, P. Kearney, S. Kauppinen, Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver. Nucleic Acids Res. 36, 1153-1162 (2008).