Improved specificity of gene silencing by siRNAs containing unlocked nucleobase analogs

Nucleic Acids Research

Volumn 39, Issue 5, 2011, Pages 1823-1832

  Vaish, Narendra ^a   Chen, Feng ^a   Seth, Shaguna ^a   Fosnaugh, Kathy ^a   Liu, Yan ^a   Adami, Roger ^a   Brown, Tod ^a   Chen, Yan ^a   Harvie, Pierrot ^a   Johns, Rachel ^a   Severson, Gregory ^a   Granger, Brian ^a   Charmley, Patrick ^a   Houston, Michael ^a   Templin, Michael V ^a   Polisky, Barry ^a  

^a Marina Biotech Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MICRORNA; NUCLEIC ACID BASE; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; UNLOCKED NUCLEOBASE DERIVATIVE;

ARTICLE; CONTROLLED STUDY; DNA BASE COMPOSITION; DNA MODIFICATION; DNA STRAND; DOWN REGULATION; GENE ACTIVITY; GENE SILENCING; GENE TARGETING; HUMAN; HUMAN CELL; NUCLEIC ACID BASE SUBSTITUTION; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; RNA ANALYSIS; TERMINAL SEQUENCE;

CELL LINE; GENE EXPRESSION PROFILING; HUMANS; MICRORNAS; RNA INTERFERENCE; RNA, SMALL INTERFERING;

EID: 79953144826     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkq961     Document Type: Article

References (25)

1. Jackson A.L. and Linsley P.S. (2010) Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application. Nat. Rev. Drug Discov. 9 57-67.
2. Langkjær N. Pasternak A. and Wengel J. (2009) UNA (unlocked nucleic acid): A flexible RNA mimic that allows engineering of nucleic acid duplex stability. Bioorg. Med. Chem. 17 5420-5425.
3. Bramsen J.B. Laursen M.B. Nielsen A.F. Hansen T.B. Bus C. Langkjaer N. Babu B.R. Hojland T. Abramov M. Van Aerschot A. 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.
4. Kenski D.M. Cooper A.J. Li J.J. Willingham A.T. Haringsma H.J. Young T.A. Kuklin N.A. Jones J.J. Cancilla M.T. McMasters D.R. et al. (2010) Analysis of acyclic nucleoside modifications in siRNAs finds sensitivity at position 1 that is restored by 50-terminal phosphorylation both in vitro and in vivo. Nucleic Acids Res. 38 660-671.
5. Laursen M.B. Pakula M.M. Gao S. Fluiter K. Mook O.R. Baas F. Langklær N. Wengel S.L. Wengel J. Kjemsab J. et al. (2010) Utilization of unlocked nucleic acid (UNA) to enhance siRNA performance in vitro and in vivo. Molecular BioSystems 6 862-870.
6. Jackson A.L. Bartz S.R. Schelter J. Kobayashi S.V. Burchard J. Mao M. Li B. Cavet G. and Linsley P.S. (2003) Expression profiling reveals off-target gene regulation by RNAi. Nature Biotechnol. 21 635-637. (Pubitemid 36638089)
7. Jackson A.L. Burchard J. Schelter J. Chau B.N. Cleary M. Lim L. and Linsley P.S. (2006) Widespread siRNA "off-target" transcript silencing mediated by seed region sequence complementarity. RNA 12 1179-1187. (Pubitemid 43990543)
8. Zeng Y. Yi R. and Cullen B.R. (2003) MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc. Natl Acad. Sci. USA 100 9779-9784. (Pubitemid 37087018)
9. Lewis B.P. Burge C.B. and Bartel D.P. (2005) Conserved seed pairing often flanked by adenosines indicates that thousands of human genes are microRNA targets. Cell 120 15-20. (Pubitemid 40094598)
10. Naito Y. Yoshimura J. Morishita S. and Ui-Tei K. (2009) siDirect 2.0: updated software for designing functional siRNA with reduced seed-dependent off-target effect. BMC Bioinformatics 10 392.
11. Birmingham A. Anderson E. Sullivan K. Reynolds A. Boese Q. Leake D. Karpilow J. and Khvorova A. (2007) A protocol for designing siRNAs with high functionality and specificity. Nat. Protoc. 2 2068-2078. (Pubitemid 351565844)
12. Jackson A.L. Burchard J. Leake D. Reynolds A. Schelter J. Guo J. Johnson J.M. Lim L. Karpilow J. Nichols K. et al. (2006) Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing. RNA 12 1197-1205. (Pubitemid 43990545)
13. Chen P.Y. Weinmann L. Gaidatzis D. Pei Y. Zavolan M. Tuschl T. and Meister G. (2008) Strand-specific 50-O-methylation of siRNA duplexes controls guide strand selection and targeting specificity. RNA 14 263-274. (Pubitemid 351171587)
14. Bramsen J.B. Laursen M.B. Damgaard C.K. Lena S.W. Babu B.R. Wengel J. and Kjems J. (2007) Improved silencing properties using small internally segmented interfering RNAs. Nucleic Acids Res. 35 5886-5897. (Pubitemid 47506303)
15. Hossbach M. Gruber J. Osborn M. Weber K. and Tuschl T. (2006) Gene silencing with siRNA duplexes composed of target-mRNA-complementary and partially palindromic or partially complementary single-stranded siRNAs. RNA Biol. 3 82-89. (Pubitemid 44444598)
16. Sun X. Rogoff H.A. and Li C.J. (2008) Asymmetric RNA duplexes mediate RNA interference in mammalian cells. Nat. Biotechnol. 26 1379-1382.
17. Ui-Tei K. Naito Y. Zenno S. Nishi K. Yamato K. Takahashi F. Juni A. and Saigo K. (2008) Functional dissection of siRNA sequence by systematic DNA substitution: modified siRNA with a DNA seed arm is a powerful tool for mammalian gene silencing with significantly reduced off-target effect. Nucleic Acids Res. 36 2136-2151. (Pubitemid 351566989)
18. Bramsen J.B. Pakula M.M. Hansen T.B. Bus C. Langkjaer N. Odadzic D. Smicius R. Wengel S.L. Chattopadhyaya J. Engels J.W. 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.
19. Semizarov D. Frost L. Sarthy A. Kroeger P. Halbert D.N. and Fesik S.W. (2003) Specificity of short interfering RNA determined through gene expression signatures. Proc. Natl Acad. Sci. USA 100 6347-6352. (Pubitemid 36666584)
20. Ui-Tei K. Naito Y. Nishi K. Juni A. and Saigo K. (2008) Thermodynamic stability and Watson-Crick base pairing in the seed duplex are major determinants of the efficiency of the siRNA-based off-target effect. Nucleic Acids Res. 36 7100-7109.
21. Lin X. Ruan X. Anderson M.G. McDowell J.A. Kroeger P.E. Fesik S.W. and Shen Y. (2005) siRNA-mediated off-target gene silencing triggered by a 7 nt complementation. Nucleic Acids Res. 33 4527-4535. (Pubitemid 41222567)
22. Gentleman R.C. Carey V.J. Bates D.M. Bolstad B. Dettling M. Dudoit S. Ellis B. Gautier L. Ge Y. Gentry J. et al. (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 5 R80.
23. Wu Z. Irizarry R.A. Gentleman R. Murillo F.M. and Spencer F. (2004) A model based background adjustment for oligonucleotide expression arrays. J. Am. Stat. Assoc. 99 909-917. (Pubitemid 39665934)
24. Smyth G.K. (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol. 3 Article3.
25. Markham N.R. and Zuker M. (2005) DINAMelt web server for nucleic acid melting prediction. Nucleic Acids Res. 33 W577-W581. (Pubitemid 44529988)