Evaluation of the effects of chemically different linkers on hepatic accumulations, cell tropism and gene silencing ability of cholesterol-conjugated antisense oligonucleotides

Journal of Controlled Release

Volumn 226, Issue , 2016, Pages 57-65

  Wada, Shunsuke ^a,b   Yasuhara, Hidenori ^a,b   Wada, Fumito ^a,b   Sawamura, Motoki ^a,b   Waki, Reiko ^a   Yamamoto, Tsuyoshi ^a,b   Harada Shiba, Mariko ^b   Obika, Satoshi ^a  

^a OSAKA UNIVERSITY   (Japan)

^b NATIONAL CEREBRAL AND CARDIOVASCULAR CENTER   (Japan)

Author keywords

Antisense oligonucleotide; Cholesterol conjugation; Linkage

Indexed keywords

CELLS; COVALENT BONDS; CYCLOHEXANE; CYTOLOGY; ESTERS; LIVER; OLIGONUCLEOTIDES; PLATELETS; TOXICITY;

ANTISENSE OLIGONUCLEOTIDES; DISULFIDE BONDS; GENE SILENCING; INHIBITORY EFFECT; LINKAGE; PARENCHYMAL CELLS; PHOSPHODIESTER BONDS; PHOSPHOROTHIOATES;

CHOLESTEROL;

ANTISENSE OLIGONUCLEOTIDE; CHOLESTEROL; CHOLESTEROL ANTISENSE OLIGONUCLEOTIDE CONJUGATE; ESTER; HEXAMETHYLENE SUCCINIMIDE; MESSENGER RNA; PHOSPHODIESTER; PHOSPHOROTHIOIC ACID; SUCCINIMIDE DERIVATIVE; UNCLASSIFIED DRUG; PCSK9 PROTEIN, MOUSE; PROPROTEIN CONVERTASE 9;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELLULAR DISTRIBUTION; CHEMICAL BOND; CONTROLLED STUDY; DISSEMINATED INTRAVASCULAR CLOTTING; DISULFIDE BOND; DRUG ACCUMULATION; DRUG CONJUGATION; DRUG DELIVERY SYSTEM; DRUG EFFECT; DRUG EFFICACY; DRUG MEGADOSE; DRUG RELEASE; DRUG SCREENING; DRUG STRUCTURE; GENE; GENE EXPRESSION; GENE SILENCING; LIVER; LIVER CELL; LIVER TOXICITY; MALE; MOUSE; NEPHROTOXICITY; NONHUMAN; PCSK9 GENE; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION; THROMBOCYTE COUNT; TROPISM; ANALOGS AND DERIVATIVES; ANIMAL; C57BL MOUSE; CHEMISTRY; GENETICS; METABOLISM;

ANIMALS; CHOLESTEROL; GENE SILENCING; LIVER; MALE; MICE, INBRED C57BL; OLIGONUCLEOTIDES, ANTISENSE; PROPROTEIN CONVERTASE 9; RNA, MESSENGER;

EID: 84958183308     PISSN: 01683659     EISSN: 18734995     Source Type: Journal    
DOI: 10.1016/j.jconrel.2016.02.007     Document Type: Article

References (37)

1. A.S. Wierzbicki, A. Viljoen, T.C. Hardman, and D.P. Mikhailidis New therapies to reduce low-density lipoprotein cholesterol Curr. Opin. Cardiol. 28 2013 452 457
2. M.J. Graham, R.G. Lee, T.A. Bell III, W. Fu, A.E. Mullick, V.J. Alexander, W. Singleton, N. Viney, R. Geary, J.Q. Su, B.F. Baker, J. Burkey, S.T. Crooke, and R.M. Crooke Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans Circ. Res. 2013
3. R.G. Lee, J. Crosby, B.F. Baker, M.J. Graham, and R.M. Crooke Antisense technology: An emerging platform for cardiovascular disease therapeutics J. Cardiovasc. Transl. Res. 6 2013 969 980
4. L. Meng, A.J. Ward, S. Chun, C.F. Bennett, A.L. Beaudet, and F. Rigo Towards a therapy for angelman syndrome by targeting a long non-coding RNA Nature 2014
5. X. Ming Cellular delivery of siRNA and antisense oligonucleotides via receptor-mediated endocytosis Expert Opin. Drug Deliv. 8 2011 435 449
6. S. Grijalvo, A. Avino, and R. Eritja Oligonucleotide delivery: A patent review (2010 - 2013) Expert Opin. Ther. Pat. 24 2014 801 819
7. K.T. Love, K.P. Mahon, C.G. Levins, K.A. Whitehead, W. Querbes, J.R. Dorkin, J. Qin, W. Cantley, L.L. Qin, T. Racie, M. Frank-Kamenetsky, K.N. Yip, R. Alvarez, D.W. Sah, A. de Fougerolles, K. Fitzgerald, V. Koteliansky, A. Akinc, R. Langer, and D.G. Anderson Lipid-like materials for low-dose, in vivo gene silencing Proc. Natl. Acad. Sci. U. S. A. 107 2010 1864 1869
8. S. Wada, S. Obika, M.A. Shibata, T. Yamamoto, M. Nakatani, T. Yamaoka, H. Torigoe, and M. Harada-Shiba Development of a 2′,4′-BNA/LNA-based siRNA for dyslipidemia and assessment of the effects of its chemical modifications In vivo Mol. Ther. Nucleic Acids 1 2012 e45
9. B. Yu, Y. Mao, L.Y. Bai, S.E. Herman, X. Wang, A. Ramanunni, Y. Jin, X. Mo, C. Cheney, K.K. Chan, D. Jarjoura, G. Marcucci, R.J. Lee, J.C. Byrd, L.J. Lee, and N. Muthusamy Targeted nanoparticle delivery overcomes off-target immunostimulatory effects of oligonucleotides and improves therapeutic efficacy in chronic lymphocytic leukemia Blood 121 2013 136 147
10. K. Nishina, T. Unno, Y. Uno, T. Kubodera, T. Kanouchi, H. Mizusawa, and T. Yokota Efficient in vivo delivery of siRNA to the liver by conjugation of alpha-tocopherol Mol. Ther. 16 2008 734 740
11. J. Soutschek, A. Akinc, B. Bramlage, K. Charisse, R. Constien, M. Donoghue, S. Elbashir, A. Geick, P. Hadwiger, J. Harborth, M. John, V. Kesavan, G. Lavine, R.K. Pandey, T. Racie, K.G. Rajeev, I. Rohl, I. Toudjarska, G. Wang, S. Wuschko, D. Bumcrot, V. Koteliansky, S. Limmer, M. Manoharan, and H.P. Vornlocher Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs Nature 432 2004 173 178
12. J. Krutzfeldt, N. Rajewsky, R. Braich, K.G. Rajeev, T. Tuschl, M. Manoharan, and M. Stoffel Silencing of microRNAs in vivo with 'antagomirs' Nature 438 2005 685 689
13. B.R. Meade, K. Gogoi, A.S. Hamil, C. Palm-Apergi, A.V. Berg, J.C. Hagopian, A.D. Springer, A. Eguchi, A.D. Kacsinta, C.F. Dowdy, A. Presente, P. Lonn, M. Kaulich, N. Yoshioka, E. Gros, X.S. Cui, and S.F. Dowdy Efficient delivery of RNAi prodrugs containing reversible charge-neutralizing phosphotriester backbone modifications Nat. Biotechnol. 2014
14. B.P. Monia, J.F. Johnston, H. Sasmor, and L.L. Cummins Nuclease resistance and antisense activity of modified oligonucleotides targeted to Ha-ras J. Biol. Chem. 271 1996 14533 14540
15. S.P. Henry, J.E. Zuckerman, J. Rojko, W.C. Hall, R.J. Harman, D. Kitchen, and S.T. Crooke Toxicological properties of several novel oligonucleotide analogs in mice Anticancer Drug Des. 12 1997 1 14
16. R. Reshat, C.C. Priestley, and N.J. Gooderham Mutagenesis by an antisense oligonucleotide and its degradation product Toxicol. Sci. 130 2012 319 327
17. S.M. Freier, and K.H. Altmann The ups and downs of nucleic acid duplex stability: structure-stability studies on chemically-modified DNA:RNA duplexes Nucleic Acids Res. 25 1997 4429 4443
18. R.S. Geary, T.A. Watanabe, L. Truong, S. Freier, E.A. Lesnik, N.B. Sioufi, H. Sasmor, M. Manoharan, and A.A. Levin Pharmacokinetic properties of 2′-O-(2-methoxyethyl)-modified oligonucleotide analogs in rats J. Pharmacol. Exp. Ther. 296 2001 890 897
19. R.L. Letsinger, G.R. Zhang, D.K. Sun, T. Ikeuchi, and P.S. Sarin Cholesteryl-conjugated oligonucleotides: synthesis, properties, and activity as inhibitors of replication of human immunodeficiency virus in cell culture Proc. Natl. Acad. Sci. U. S. A. 86 1989 6553 6556
20. S.T. Crooke, M.J. Graham, J.E. Zuckerman, D. Brooks, B.S. Conklin, L.L. Cummins, M.J. Greig, C.J. Guinosso, D. Kornbrust, M. Manoharan, H.M. Sasmor, T. Schleich, K.L. Tivel, and R.H. Griffey Pharmacokinetic properties of several novel oligonucleotide analogs in mice J. Pharmacol. Exp. Ther. 277 1996 923 937
21. H. Mukai, D. Ozaki, Y. Cui, T. Kuboyama, H. Yamato-Nagata, K. Onoe, M. Takahashi, Y. Wada, T. Imanishi, T. Kodama, S. Obika, M. Suzuki, H. Doi, and Y. Watanabe Quantitative evaluation of the improvement in the pharmacokinetics of a nucleic acid drug delivery system by dynamic PET imaging with (18)F-incorporated oligodeoxynucleotides J. Control. Release 180 2014 92 99
22. S.K. Srinivasan, H.K. Tewary, and P.L. Iversen Characterization of binding sites, extent of binding, and drug interactions of oligonucleotides with albumin Antisense Res. Dev. 5 1995 131 139
23. M.K. Bijsterbosch, E.T. Rump, R.L. De Vrueh, R. Dorland, R. van Veghel, K.L. Tivel, E.A. Biessen, T.J. van Berkel, and M. Manoharan Modulation of plasma protein binding and in vivo liver cell uptake of phosphorothioate oligodeoxynucleotides by cholesterol conjugation Nucleic Acids Res. 28 2000 2717 2725
24. M.K. Bijsterbosch, M. Manoharan, R. Dorland, I.H. Waarlo, E.A. Biessen, and T.J. van Berkel Delivery of cholesteryl-conjugated phosphorothioate oligodeoxynucleotides to kupffer cells by lactosylated low-density lipoprotein Biochem. Pharmacol. 62 2001 627 633
25. M.K. Bijsterbosch, M. Manoharan, R. Dorland, R. Van Veghel, E.A. Biessen, and T.J. Van Berkel Bis-cholesteryl-conjugated phosphorothioate oligodeoxynucleotides are highly selectively taken up by the liver J. Pharmacol. Exp. Ther. 302 2002 619 626
26. K. Cheng, Z. Ye, R.V. Guntaka, and R.I. Mahato Enhanced hepatic uptake and bioactivity of type alpha1(I) collagen gene promoter-specific triplex-forming oligonucleotides after conjugation with cholesterol J. Pharmacol. Exp. Ther. 317 2006 797 805
27. C.A. Stein, J.B. Hansen, J. Lai, S. Wu, A. Voskresenskiy, A. Hog, J. Worm, M. Hedtjarn, N. Souleimanian, P. Miller, H.S. Soifer, D. Castanotto, L. Benimetskaya, H. Orum, and T. Koch Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents Nucleic Acids Res. 38 2010 e3
28. L. Wang, J. Kristensen, and D.E. Ruffner Delivery of antisense oligonucleotides using HPMA polymer: synthesis of A thiol polymer and its conjugation to water-soluble molecules Bioconjug. Chem. 9 1998 749 757
29. M. Dominska, and D.M. Dykxhoorn Breaking down the barriers: siRNA delivery and endosome escape J. Cell Sci. 123 2010 1183 1189
30. Patent: S. Obika, M. Shiba, T. Yamamoto, M. Nakatani, H. Yasuhara; Oligonucleotide, and therapeutic agent for dyslipidemia which contains oligonucleotide as active ingredient. WO2014007305A, Jan 9 2014.
31. T. Yamamoto, M. Harada-Shiba, M. Nakatani, S. Wada, H. Yasuhara, K. Narukawa, K. Sasaki, M.A. Shibata, H. Torigoe, T. Yamaoka, T. Imanishi, and S. Obika Cholesterol-lowering action of BNA-based antisense oligonucleotides targeting PCSK9 in atherogenic diet-induced hypercholesterolemic mice Mol. Ther. Nucleic Acids 1 2012 e22
32. T. Nishina, J. Numata, K. Nishina, K. Yoshida-Tanaka, K. Nitta, W. Piao, R. Iwata, S. Ito, H. Kuwahara, T. Wada, H. Mizusawa, and T. Yokota Chimeric antisense oligonucleotide conjugated to alpha-tocopherol Mol. Ther. Nucleic Acids 4 2015 e220
33. A. Zaid, A. Roubtsova, R. Essalmani, J. Marcinkiewicz, A. Chamberland, J. Hamelin, M. Tremblay, H. Jacques, W. Jin, J. Davignon, N.G. Seidah, and A. Prat Proprotein convertase subtilisin/kexin type 9 (PCSK9): hepatocyte-specific low-density lipoprotein receptor degradation and critical role in mouse liver regeneration Hepatology 48 2008 646 654
34. M.E. Ostergaard, J. Yu, G.A. Kinberger, W.B. Wan, M.T. Migawa, G. Vasquez, K. Schmidt, H.J. Gaus, H.M. Murray, A. Low, E.E. Swayze, T.P. Prakash, and P.P. Seth Efficient synthesis and biological evaluation of 5′-GalNAc conjugated antisense oligonucleotides Bioconjug. Chem. 26 2015 1451 1455
35. J. Desjardins, J. Mata, T. Brown, D. Graham, G. Zon, and P. Iversen Cholesteryl-conjugated phosphorothioate oligodeoxynucleotides modulate CYP2B1 expression in vivo J. Drug Target. 2 1995 477 485
36. U. Flierl, T.L. Nero, B. Lim, J.F. Arthur, Y. Yao, S.M. Jung, E. Gitz, A.Y. Pollitt, M.T. Zaldivia, M. Jandrot-Perrus, A. Schafer, B. Nieswandt, R.K. Andrews, M.W. Parker, E.E. Gardiner, and K. Peter Phosphorothioate backbone modifications of nucleotide-based drugs are potent platelet activators J. Exp. Med. 212 2015 129 137
37. E.M. Straarup, N. Fisker, M. Hedtjarn, M.W. Lindholm, C. Rosenbohm, V. Aarup, H.F. Hansen, H. Orum, J.B. Hansen, and 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 2010 7100