Development of a 2',4'-BNA/LNA-based siRNA for dyslipidemia and assessment of the effects of its chemical modifications in vivo

Molecular Therapy Nucleic Acids

Volumn 1, Issue 9, 2012, Pages e45-

  Wada, Shunsuke ^a,b   Obika, Satoshi ^c   Shibata, Masa Aki ^d   Yamamoto, Tsuyoshi ^a,c   Nakatani, Moeka ^a,c   Yamaoka, Tetsuji ^a   Torigoe, Hidetaka ^b   Harada Shiba, Mariko ^a  

^a NATIONAL CEREBRAL AND CARDIOVASCULAR CENTER   (Japan)

^b TOKYO UNIVERSITY OF SCIENCE   (Japan)

^c OSAKA UNIVERSITY   (Japan)

^d OSAKA HEALTH SCIENCE UNIVERSITY   (Japan)

Author keywords

2'4' BNA LNA; Chemical modification; Dyslipidemia; Innate immune response; SiRNA

Indexed keywords

EID: 84868351331     PISSN: None     EISSN: 21622531     Source Type: Journal    
DOI: 10.1038/mtna.2012.32     Document Type: Article

References (46)

1. Hannon, GJ (2002). RNA interference. Nature 418: 244-251. (Pubitemid 34773784)
2. McManus, MT and Sharp, PA (2002). Gene silencing in mammals by small interfering RNAs. Nat Rev Genet 3: 737-747.
3. White, PJ (2008). Barriers to successful delivery of short interfering RNA after systemic administration. Clin Exp Pharmacol Physiol 35: 1371-1376.
4. Chiu, YL and Rana, TM (2003). siRNA function in RNAi: a chemical modification analysis. RNA 9: 1034-1048. (Pubitemid 37093614)
5. De Paula, D, Bentley, MV and Mahato, RI (2007). Hydrophobization and bioconjugation for enhanced siRNA delivery and targeting. RNA 13: 431-456. (Pubitemid 46509424)
6. Shim, MS and Kwon, YJ (2010). Efficient and targeted delivery of siRNA in vivo. FEBS J 277: 4814-4827.
7. Davidson, BL and McCray, PB Jr (2011). Current prospects for RNA interference-based therapies. Nat Rev Genet 12: 329-340.
8. Kuwahara, H, Nishina, K, Yoshida, K, Nishina, T, Yamamoto, M, Saito, Y et al. (2011). Efficient in vivo delivery of siRNA into brain capillary endothelial cells along with endogenous lipoprotein. Mol Ther 19: 2213-2221.
9. Semple, SC, Akinc, A, Chen, J, Sandhu, AP, Mui, BL, Cho, CK et al. (2010). Rational design of cationic lipids for siRNA delivery. Nat Biotechnol 28: 172-176.
10. Love, KT, Mahon, KP, Levins, CG, Whitehead, KA, Querbes, W, Dorkin, JR et al. (2010). Lipid-like materials for low-dose, in vivo gene silencing. Proc Natl Acad Sci USA 107: 1864-1869.
11. Ge, Q, Dallas, A, Ilves, H, Shorenstein, J, Behlke, MA and Johnston, BH (2010). Effects of chemical modification on the potency, serum stability, and immunostimulatory properties of short shRNAs. RNA 16: 118-130.
12. Chernolovskaya, EL and Zenkova, MA (2010). Chemical modification of siRNA. Curr Opin Mol Ther 12: 158-167.
13. Obika, S, Rahman, SMA, Fujisaka, A, Kawada, Y, Baba, T, and Imanishi, T (2010). Bridged nucleic acids: development, synthesis and properties. Heterocycles 81: 1347-1392.
14. Imanishi, T, and Obika, S (2002). BNAs: novel nucleic acid analogus with a bridged sugar moiety. ChemComm: 6.
15. Elmén, J, Thonberg, H, Ljungberg, K, Frieden, M, Westergaard, M, Xu, Y et al. (2005). Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality. Nucleic Acids Res 33: 439-447. (Pubitemid 40276964)
16. Bramsen, JB, Laursen, MB, Damgaard, CK, Lena, SW, Babu, BR, Wengel, J et al. (2007). Improved silencing properties using small internally segmented interfering RNAs. Nucleic Acids Res 35: 5886-5897. (Pubitemid 47506303)
17. Bramsen, JB, Pakula, MM, Hansen, TB, Bus, C, Langkjær, N, Odadzic, D et al. (2010). A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects. Nucleic Acids Res 38: 5761-5773.
18. Bramsen, JB, Laursen, MB, Nielsen, AF, Hansen, TB, Bus, C, Langkjaer, N et al. (2009). A large-scale chemical modification screen identifies design rules to generate siRNAs with high activity, high stability and low toxicity. Nucleic Acids Res 37: 2867-2881.
19. Abdur Rahman, SM, Sato, H, Tsuda, N, Haitani, S, Narukawa, K, Imanishi, T et al. (2010). RNA interference with 2?,4?-bridged nucleic acid analogues. Bioorg Med Chem 18: 3474-3480.
20. Jurk, M, Chikh, G, Schulte, B, Kritzler, A, Richardt-Pargmann, D, Lampron, C et al. (2011). Immunostimulatory potential of silencing RNAs can be mediated by a non-uridine-rich toll-like receptor 7 motif. Nucleic Acid Ther 21: 201-214.
21. Allerson, CR, Sioufi, N, Jarres, R, Prakash, TP, Naik, N, Berdeja, A et al. (2005). Fully 2'-modified oligonucleotide duplexes with improved in vitro potency and stability compared to unmodified small interfering RNA. J Med Chem 48: 901-904. (Pubitemid 40270434)
22. Samuel-Abraham, S and Leonard, JN (2010). Staying on message: design principles for controlling nonspecific responses to siRNA. FEBS J 277: 4828-4836.
23. Goldstein, JL (2001). Laskers for 2001: knockout mice and test-tube babies. Nat Med 7: 1079-1080. (Pubitemid 33010003)
24. Durrington, P (2003). Dyslipidaemia. Lancet 362: 717-731. (Pubitemid 37101072)
25. Soutschek, J, Akinc, A, Bramlage, B, Charisse, K, Constien, R, Donoghue, M et al. (2004). Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432: 173-178. (Pubitemid 39545841)
26. Khvorova, A, Reynolds, A and Jayasena, SD (2003). Functional siRNAs and miRNAs exhibit strand bias. Cell 115: 209-216. (Pubitemid 37329584)
27. Schwarz, DS, Hutvágner, G, Du, T, Xu, Z, Aronin, N and Zamore, PD (2003). Asymmetry in the assembly of the RNAi enzyme complex. Cell 115: 199-208. (Pubitemid 37329583)
28. Kennedy, S, Wang, D and Ruvkun, G (2004). A conserved siRNA-degrading RNase negatively regulates RNA interference in C. elegans. Nature 427: 645-649. (Pubitemid 38248485)
29. Volkov, AA, Kruglova, NS, Meschaninova, MI, Venyaminova, AG, Zenkova, MA, Vlassov, VV et al. (2009). Selective protection of nuclease-sensitive sites in siRNA prolongs silencing effect. Oligonucleotides 19: 191-202.
30. Mook, OR, Baas, F, de Wissel, MB and Fluiter, K (2007). Evaluation of locked nucleic acid-modified small interfering RNA in vitro and in vivo. Mol Cancer Ther 6: 833-843. (Pubitemid 46554553)
31. Liu, L, Botos, I, Wang, Y, Leonard, JN, Shiloach, J, Segal, DM et al. (2008). Structural basis of toll-like receptor 3 signaling with double-stranded RNA. Science 320: 379-381. (Pubitemid 351555661)
32. Judge, AD, Bola, G, Lee, AC and MacLachlan, I (2006). Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo. Mol Ther 13: 494-505. (Pubitemid 43257617)
33. Hornung, V, Guenthner-Biller, M, Bourquin, C, Ablasser, A, Schlee, M, Uematsu, S et al. (2005). Sequence-specific potent induction of IFN-α by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat Med 11: 263-270. (Pubitemid 40460553)
34. McCarroll, J, Baigude, H, Yang, CS and Rana, TM (2010). Nanotubes functionalized with lipids and natural amino acid dendrimers: a new strategy to create nanomaterials for delivering systemic RNAi. Bioconjug Chem 21: 56-63.
35. Aronin, N (2006). Target selectivity in mRNA silencing. Gene Ther 13: 509-516.
36. Jackson, AL, Burchard, J, Leake, D, Reynolds, A, Schelter, J, Guo, J et al. (2006). Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing. RNA 12: 1197-1205. (Pubitemid 43990545)
37. Carthew, RW and Sontheimer, EJ (2009). Origins and Mechanisms of miRNAs and siRNAs. Cell 136: 642-655.
38. Matranga, C, Tomari, Y, Shin, C, Bartel, DP and Zamore, PD (2005). Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 123: 607-620. (Pubitemid 41608464)
39. Leuschner, PJ, Ameres, SL, Kueng, S and Martinez, J (2006). Cleavage of the siRNA passenger strand during RISC assembly in human cells. EMBO Rep 7: 314-320.
40. Rossi, JJ (2009). Cholesterol paves the way for topically applied viricides. Cell Host Microbe 5: 6-7.
41. Ambardekar, VV, Han, HY, Varney, ML, Vinogradov, SV, Singh, RK and Vetro, JA (2011). The modification of siRNA with 3' cholesterol to increase nuclease protection and suppression of native mRNA by select siRNA polyplexes. Biomaterials 32: 1404-1411.
42. Haley, B and Zamore, PD (2004). Kinetic analysis of the RNAi enzyme complex. Nat Struct Mol Biol 11: 599-606. (Pubitemid 38823525)
43. Marques, JT, Devosse, T, Wang, D, Zamanian-Daryoush, M, Serbinowski, P, Hartmann, R et al. (2006). A structural basis for discriminating between self and nonself doublestranded RNAs in mammalian cells. Nat Biotechnol 24: 559-565.
44. Kato, H, Takeuchi, O, Mikamo-Satoh, E, Hirai, R, Kawai, T, Matsushita, K et al. (2008). Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J Exp Med 205: 1601-1610. (Pubitemid 351962024)
45. Gao, S, Dagnaes-Hansen, F, Nielsen, EJ, Wengel, J, Besenbacher, F, Howard, KA et al. (2009). The effect of chemical modification and nanoparticle formulation on stability and biodistribution of siRNA in mice. Mol Ther 17: 1225-1233.
46. Caffrey, DR, Zhao, J, Song, Z, Schaffer, ME, Haney, SA, Subramanian, RR et al. (2011). siRNA off-target effects can be reduced at concentrations that match their individual potency. PLoS ONE 6: e21503.