Applications of mass spectrometry to the study of siRNA

Mass Spectrometry Reviews

Volumn 30, Issue 6, 2011, Pages 979-998

  Beverly, Michael B ^a,b  

^a MERCK RESEARCH LABORATORIES   (United States)

^b NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

Author keywords

Mass spectrometry; miRNA; RNA interference; RNAi; siRNA

Indexed keywords

ANALYTICAL TECHNIQUES; DOUBLE-STRANDED RNA; ELECTROSPRAYS; MIRNA; RNA INTERFERENCE; RNAI; SIRNA; THERAPEUTIC POTENTIALS;

GENE EXPRESSION; GENE EXPRESSION REGULATION; MASS SPECTROMETRY; OLIGONUCLEOTIDES; RNA;

GENE THERAPY;

DOUBLE STRANDED RNA; MICRORNA; OLIGONUCLEOTIDE; SMALL INTERFERING RNA;

ARTICLE; CHEMISTRY; ELECTROSPRAY MASS SPECTROMETRY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; METHODOLOGY; PHYSIOLOGY; RNA INTERFERENCE;

CHROMATOGRAPHY, HIGH PRESSURE LIQUID; MICRORNAS; OLIGONUCLEOTIDES; RNA INTERFERENCE; RNA, DOUBLE-STRANDED; RNA, SMALL INTERFERING; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; SPECTROMETRY, MASS, MATRIX-ASSISTED LASER DESORPTION-IONIZATION;

EID: 82955220505     PISSN: 02777037     EISSN: 10982787     Source Type: Journal    
DOI: 10.1002/mas.20260     Document Type: Article

References (161)

1. Alisky JM, Davidson BL. 2004. Towards therapy using RNA interference. Am J Pharmacogenomics 4:45-51.
2. Ameres SL, Martinez J, Schroeder R. 2007. Molecular basis for target RNA recognition and cleavage by human RISC. Cell 130:101-112.
3. Apffel A, Chakel J, Fischer S, Lichtenwalter K, HancockW. 1997a. Analysis of oligonucleotides by HPLC-electrospray ionization mass spectrometry. Anal Chem 69:1320-1325.
4. Apffel A, Chakel J, Fischer S, Lichtenwalter K, Hancock W. 1997b. New procedure for the use of high-performance liquid chromatographyelectrospray ionization mass spectrometry for the analysis of nucleotides and oligonucleotides. J Chromatogr A 777:3-21.
5. Asara JM, Allison J. 1999. Enhanced detection of oligonucleotides in UV MALDI MS using the tetraamine spermine as a matrix additive. Anal Chem 71:2866-2870.
6. Baba Y. 1993. Prediction of the behaviour of oligonucleotides in highperformance liquid chromatography and capillary electrophoresis. J Chromatogr 618:41-55.
7. Bahr U, Aygun H, Karas M. 2008. Detection and relative quantification of siRNA double strands by MALDI mass spectrometry. Anal Chem 80: 6280-6285.
8. Bahr U, Aygun H, Karas M. 2009. Sequencing of single and double stranded RNA oligonucleotides by acid hydrolysis and MALDI mass spectrometry. Anal Chem 81:3173-3179.
9. Banoub JH, Newton RP, Esmans E, Ewing DF, Mackenzie G. 2005. Recent developments in mass spectrometry for the characterization of nucleosides, nucleotides, oligonucleotides, and nucleic acids. Chem Rev 105: 1869-1915.
10. Barik S. 2004. Development of gene-specific double-stranded RNA drugs. Ann Med 36:540-551.
11. Bartha A, Stahlberg J. 1994. Electrostatic retention model of reversed-phase ion-pair chromatography. J Chromatogr A 668:255-284.
12. Bayer E, Bauer T, Schmeer K, Bleicher K, Maier M, Gaus HJ. 1994. Analysis of double-stranded oligonucleotides by electrospray mass spectrometry. Anal Chem 66:3858-3863.
13. Beck J, Colgrave M, Ralph S, Sheil M. 2001. Electrospray ionization mass spectrometry of oligonucleotide complexes with drugs, metals and proteins. Mass Spectrom Rev 20:61-87.
14. Behlke MA. 2008. Chemical modification of siRNAs for in vivo use. Oligonucleotides 18:305-320.
15. Beverly M, Hartsough K, Machemer L. 2005. Liquid chromatography/ electrospray mass spectrometric analysis of metabolites from an inhibitory RNA duplex. Rapid Commun Mass Spectrom 19:1675-1682.
16. Beverly M, Hartsough K, Machemer L, Pavco P, Lockridge J. 2006. Liquid chromatography electrospray ionization mass spectrometry analysis of the ocular metabolites from a short interfering RNA duplex. J Chromatogr B Analyt Technol Biomed Life Sci 835:62-70.
17. Bleicher K, Bayer E. 1994. Analysis of oligonucleotides using coupled high performance liquid chromatography-electrospray mass spectrometry. Chromatographia 39:405-408.
18. Braasch DA, Jensen S, Liu Y, Kaur K, Arar K, White MA, Corey DR. 2003. RNA interference in mammalian cells by chemically-modified RNA. Biochemistry 42:7967-7975.
19. Buncek M, Backovska V, Holasova S, Radilova H, Safarova M, Kunc F, Haluza R. 2006. Unusual chromatographic behavior of oligonucleotide sequence isomers on two different anion exchange HPLC columns. Anal Biochem 348:300-306.
20. Capaldi DC, Gaus HJ, Carty RL, Moore MN, Turney BJ, Decottignies SD, McArdle JV, Scozzari AN, Ravikumar VT, Krotz AH. 2004. Formation of 4,40-dimethoxytrityl-C-phosphonate oligonucleotides. Bioorg Med Chem Lett 14:4683-4690.
21. Cavanagh J, Benson LM, Thompson R, Naylor S. 2003. In-line desalting mass spectrometry for the study of noncovalent biological complexes. Anal Chem 75:2949-2954.
22. Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, Lao KQ, Livak KJ, Guegler KJ. 2005. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 33:e179.
23. Cheng A, Li M, Liang Y,Wang Y,Wong L, Chen C, Vlassov AV, Magdaleno S. 2009. Stem-loop RT-PCR quantification of siRNAs in vitro and in vivo. Oligonucleotides 19:203-208.
24. Cissell KA, RahimiY, Shrestha S, Hunt EA, Deo SK. 2008. Bioluminescencebased detection of microRNA, miR21 in breast cancer cells. Anal Chem 80:2319-2325.
25. Crain PF, McCloskey JA. 1998. Applications of mass spectrometry to the characterization of oligonucleotides and nucleic acids. Curr Opin Biotechnol 9:25-34.
26. Currie GJ,Yates JR III. 1993. Analysis of oligodeoxynucleotides by negativeion matrix-assisted laser desorption mass spectrometry. J Am Soc Mass Spectrom 4:955-963.
27. Dai G, Wei X, Liu Z, Liu S, Marcucci G, Chan KK. 2005. Characterization and quantification of Bcl-2 antisense G3139 and metabolites in plasma and urine by ion-pair reversed phase HPLC coupled with electrospray ion-trap mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 825:201-213.
28. Dickman MJ. 2005. Effects of sequence and structure in the separation of nucleic acids using ion pair reverse phase liquid chromatography. J Chromatogr A 1076:83-89.
29. Distler AM, Allison J. 2001. 5-Methoxysalicylic acid and spermine: A new matrix for the matrix-assisted laser desorption/ionization mass spectrometry analysis of oligonucleotides. J Am Soc Mass Spectrom 12:456-462.
30. DistlerAM,Allison J. 2002. Additives for the stabilization of double-stranded DNA in UV-MALDI MS. J Am Soc Mass Spectrom 13:1129-1137.
31. Distler AM, Allison J. 2003. Stabilization of duplex oligonucleotides for analysis by matrix-assisted laser desorption/ionization mass spectrometry using the crystallographic condensing agent cobalt(III) hexamine. Anal Biochem 319:332-334.
32. Draper DE. 2004. A guide to ions and RNA structure. RNA 10:335-343.
33. Duncan DD, Eshoo M, Esau C, Freier SM, Lollo BA. 2006. Absolute quantitation of microRNAs with a PCR-based assay. AnalBiochem359:268-270.
34. Egli M, Minasov G, Tereshko V, Pallan PS, Teplova M, Inamati GB, Lesnik EA, Owens SR, Ross BS, Prakash TP, Manoharan M. 2005. Probing the influence of stereoelectronic effects on the biophysical properties of oligonucleotides: Comprehensive analysis of theRNAaffinity, nuclease resistance, and crystal structure of ten 20-O-ribonucleic acid modifications. Biochemistry 44:9045-9057.
35. Elbashir SM, Harborth J, LendeckelW, Yalcin A,Weber K, Tuschl T. 2001a. Duplexes of 21-nucleotide RNAs mediate RNAinterference in cultured mammalian cells. Nature 411:494-498.
36. Elbashir SM, Lendeckel W, Tuschl T. 2001b. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev 15:188-200.
37. Elmen J, Thonberg H, Ljungberg K, Frieden M, Westergaard M, Xu Y, Wahren B, Liang Z, Orum H, Koch T, Wahlestedt C. 2005. Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality. Nucleic Acids Res 33:439-447.
38. Elmen J, Lindow M, Schutz S, Lawrence M, Petri A, Obad S, Lindholm M, Hedtjarn M, Hansen HF, Berger U, Gullans S, Kearney P, Sarnow P, Straarup EM, Kauppinen S. 2008. LNA-mediated microRNA silencing in non-human primates. Nature. 452:896-899.
39. Farand J, Beverly M. 2008. Sequence confirmation of modified oligonucleotides using chemical degradation, electrospray ionization, time-offlight, and tandem mass spectrometry. Anal Chem 80:7414-7421.
40. Farand J, Gosselin F. 2009. De novo sequence determination of modified oligonucleotides. Anal Chem 81:3723-3730.
41. Filipowicz W. 2005. RNAi: The nuts and bolts of the RISC machine. Cell 122:17-20.
42. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. 1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806-811.
43. Fitzgerald MC, Smith LM. 1995. Mass spectrometry of nucleic acids: The promise of matrix-assisted laser desorption-ionization (MALDI) mass spectrometry. Annu Rev Biophys Biomol Struct 24:117-140.
44. Fountain KJ, Gilar M, Gebler JC. 2003. Analysis of native and chemically modified oligonucleotides by tandem ion-pair reversed-phase highperformance liquid chromatography/electrospray ionization mass spectrometry. Rapid Commun Mass Spectrom 17:646-653.
45. Fountain KJ, Gilar M, Gebler JC. 2004. Electrospray ionization mass spectrometric analysis of nucleic acids using high-throughput on-line desalting. Rapid Commun Mass Spectrom 18:1295-1302.
46. Freier SM, Altmann KH. 1997. The ups and downs of nucleic acid duplex stability: Structure-stability studies on chemically-modifiedDNA:RNA duplexes. Nucleic Acids Res 25:4429-4443.
47. Freier SM, Kierzek R, Jaeger JA, Sugimoto N, Caruthers MH, Neilson T, Turner DH. 1986. Improved free-energy parameters for predictions of RNA duplex stability. Proc Natl Acad Sci USA 83:9373-9377.
48. Fu Y, Xu S, Pan C, Ye M, Zou H, Guo B. 2006. A matrix of 3,4- diaminobenzophenone for the analysis of oligonucleotides by matrixassisted laser desorption/ionization time-of-flight mass spectrometry. Nucleic Acids Res 34:e94.
49. Gabelica V, De Pauw E. 2002. Collision-induced dissociation of 16mer DNA duplexes with various sequences: Evidence for conservation of the double helix conformation in the gas phase. Int J Mass Spectrom 219: 151-159.
50. Gabelica V, Pauw ED. 2001. Comparison between solution-phase stability and gas-phase kinetic stability of oligodeoxynucleotide duplexes. J Mass Spectrom 36:397-402.
51. Gabelica V, Rosu F, Houssier C, De Pauw E. 2000. Gas phase thermal denaturation of an oligonucleotide duplex and its complexes with minor groove binders. Rapid Commun Mass Spectrom 14:464-467.
52. Gaus H, Owens S,Winniman M, Cooper S, Cummins L. 1997. On-line HPLC electrospray mass spectrometry of phosphorothioate oligonucleotide metabolites. Anal Chem 69:313-319.
53. Gaus H, Olsen P, Sooy KV, Rentel C, Turney B, Walker KL, McArdle JV, Capaldi DC. 2005. Trichloroacetaldehyde modified oligonucleotides. Bioorg Med Chem Lett 15:4118-4124.
54. Geary RS,Watanabe TA, Truong L, Freier S, Lesnik EA, Sioufi NB, Sasmor H, Manoharan M, Levin AA. 2001. Pharmacokinetic properties of 20-O- (2-methoxyethyl)-modified oligonucleotide analogs in rats. J Pharmacol Exp Ther 296:890-897.
55. Gidden J, Baker ES, Ferzoco A, Bowers MT. 2004. Structural motifs of DNA complexes in the gas phase. Int J Mass Spectrom 240:183-193.
56. Gilar M. 2001. Analysis and purification of synthetic oligonucleotides by reversed-phase high-performance liquid chromatography with photodiode array and mass spectrometry detection. Anal Biochem 298:196-206.
57. Gilar M, Neue UD. 2007. Peak capacity in gradient reversed-phase liquid chromatography of biopolymers. Theoretical and practical implications for the separation of oligonucleotides. J Chromatogr A 1169:139-150.
58. Gilar M, Belenky A, Smisek DL, Bourque A, Cohen AS. 1997. Kinetics of phosphorothioate oligonucleotide metabolism in biological fluids. Nucleic Acids Res 25:3615-3620.
59. Gilar M, Belenky A, Budman Y, Smisek DL, Cohen AS. 1998. Study of phosphorothioate-modified oligonucleotide resistance to 30-exonuclease using capillary electrophoresis. J Chromatogr B Biomed Sci Appl 714:13-20.
60. Gilar M, Belenky A,Wang BH. 2001. High-throughput biopolymer desalting by solid-phase extraction prior to mass spectrometric analysis. J Chromatogr A 921:3-13.
61. Gilar M, Fountain KJ, Budman Y, Neue UD, Yardley KR, Rainville PD, Russell RJ II, Gebler JC. 2002. Ion-pair reversed-phase high-performance liquid chromatography analysis of oligonucleotides: Retention prediction. J Chromatogr A 958:167-182.
62. Gilar M, Fountain KJ, Budman Y, Holyoke JL, Davoudi H, Gebler JC. 2003. Characterization of therapeutic oligonucleotides using liquid chromatography with on-line mass spectrometry detection. Oligonucleotides 13:229-243.
63. Greig M, Griffey R. 1995. Utility of organic bases for improved electrospray mass spectrometry of oligonucleotides. Rapid Commun Mass Spectrom 9:97-102.
64. Griffey R, Greig M, Gaus H, Liu K, Monteith D,Winniman M, Cummins L. 1997. Characterization of oligonucleotide metabolismin vivo via liquid chromatography/electrospray tandem mass spectrometry with a quadrupole ion trap mass spectrometer. J Mass Spectrom 32:305-313.
65. Gu C, Wang Y. 2007. In vitro replication and thermodynamic studies of methylation and oxidation modifications of 6-thioguanine. Nucleic Acids Res 35:3693-3704.
66. Hernandez-Borges J, Neususs C, Cifuentes A, Pelzing M. 2004. On-line capillary electrophoresis-mass spectrometry for the analysis of biomolecules. Electrophoresis 25:2257-2281.
67. Hofstadler SA, Griffey RH. 2001. Analysis of noncovalent complexes of DNA and RNA by mass spectrometry. Chem Rev 101:377-390.
68. Hofstadler SA, Sannes-Lowery KA, Hannis JC. 2005. Analysis of nucleic acids by FTICR MS. Mass Spectrom Rev 24:265-285.
69. Holzl G, Oberacher H, Pitsch S, Stutz A, Huber CG. 2005. Analysis of biological and synthetic ribonucleic acids by liquid chromatographymass spectrometry using monolithic capillary columns. Anal Chem 77:673-680.
70. Huang TY, Liu J, Liang X, Hodges BD, McLuckey SA. 2008. Collisioninduced dissociation of intact duplex and single-stranded siRNAanions. Anal Chem 80:8501-8508.
71. Huber CG, Buchmeiser MR. 1998. On-line cation exchange for suppression of adduct formation in negative-ion electrospray mass spectrometry of nucleic acids. Anal Chem 70:5288-5295.
72. Huber CG, Oberacher H. 2001. Analysis of nucleic acids by on-line liquid chromatography-mass spectrometry. Mass Spectrom Rev 20:310-343.
73. Huber CG, Oefner PJ, Bonn GK. 1992. High-performance liquid chromatographic separation of detritylated oligonucleotides on highly crosslinked poly-(styrene-divinylbenzene) particles. J Chromatogr 599: 113-118.
74. Huber CG, Oefner PJ, Bonn GK. 1993. High-resolution liquid chromatography of oligonucleotides on nonporous alkylated styrene-divinylbenzene copolymers. Anal Biochem 212:351-358.
75. Jiang M, Arzumanov AA, Gait MJ, Milner J. 2005. A bi-functional siRNA construct induces RNA interference and also primes PCR amplification for its own quantification. Nucleic Acids Res 33:e151.
76. Jorgensen R. 1990. Altered gene expression in plants due to transinteractions between homologous genes. Trends in Biotechnol 8:340-344.
77. Jorgensen R. 2006. Plants, RNAi, and the Nobel Prize. Science 314:1242-1243.
78. Katoh T, SakaguchiY, Miyauchi K, Suzuki T, Kashiwabara S, Baba T, Suzuki T. 2009. Selective stabilization of mammalian microRNAs by 30 adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2. Genes Dev 23:433-438.
79. Khvorova A, Reynolds A, Jayasena SD. 2003. Functional siRNAs and miRNAs exhibit strand bias. Cell 115:209-216.
80. Kirpekar F, Nordhoff E, Kristiansen K, Roepstorff P, Lezius A, Hahner S, Karas M, Hillenkamp F. 1994. Matrix assisted laser desorption/ ionization mass spectrometry of enzymatically synthesized RNA up to 150 kDa. Nucleic Acids Res 22:3866-3870.
81. Kirpekar F, Berkenkamp S, Hillenkamp F. 1999. Detection of doublestranded DNA by IR- and UV-MALDI mass spectrometry. Anal Chem 71:2334-2339.
82. Kretschmer-Kazemi Far R, Sczakiel G. 2003. The activity of siRNA in mammalian cells is related to structural target accessibility: A comparison with antisense oligonucleotides. Nucleic Acids Res 31:4417-4424.
83. Kubo T, Zhelev Z, Ohba H, Bakalova R. 2007. Modified 27-nt dsRNAs with dramatically enhanced stability in serum and long-term RNAi activity. Oligonucleotides 17:445-464.
84. Kurata C, Bradley K, Gaus H, Luu N, Cedillo I, Ravikumar VT, Van Sooy K, McArdle JV, Capaldi DC. 2006. Characterization of high molecular weight impurities in synthetic phosphorothioate oligonucleotides. Bioorg Med Chem Lett 16:607-614.
85. Lavanant H, Lange C. 2002. Sodium-tolerant matrix for matrix-assisted laser desorption/ionization mass spectrometry and post-source decay of oligonucleotides. Rapid Commun Mass Spectrom 16:1928-1933.
86. Layzer JM, McCaffrey AP, Tanner AK, Huang Z, Kay MA, Sullenger BA. 2004. In vivo activity of nuclease-resistant siRNAs. RNA 10:766-771.
87. Lecchi P, Le HM, Pannell LK. 1995. 6-Aza-2-thiothymine: A matrix for MALDI spectra of oligonucleotides. Nucleic Acids Res 23:1276-1277.
88. Lesnik EA, Freier SM. 1995. Relative thermodynamic stability of DNA, RNA, and DNA:RNA hybrid duplexes: Relationship with base composition and structure. Biochemistry 34:10807-10815.
89. Lesnik EA, Guinosso CJ, Kawasaki AM, Sasmor H, Zounes M, Cummins LL, Ecker DJ, Cook PD, Freier SM. 1993. Oligodeoxynucleotides containing 20-O-modified adenosine: Synthesis and effects on stability of DNA:RNA duplexes. Biochemistry 32:7832-7838.
90. Light-Wahl K, Springer D,Winger B, Edmonds C, Camp D, Thrall B, Smith R. 1993. Observation of a small oligonucleotide duplex by electrospray ionization mass spectrometry. J Am Chem Soc 115:803-804.
91. Limbach P. 1996. Indirect mass spectrometric methods for characterizing and sequencing oligonucleotides. Mass Spectrom Rev 15:297-336.
92. Limbach PA, Crain PF, McCloskey JA. 1994. Summary: The modified nucleosides of RNA. Nucleic Acids Res 22:2183-2196.
93. Limbach PA, Crain PF, McCloskey JA. 1995a. Characterization of oligonucleotides and nucleic acids by mass spectrometry. Curr Opin Biotechnol 6:96-102.
94. Limbach PA, Crain PF, McCloskey JA. 1995b. Molecular mass measurement of intact ribonucleic acids via electrospray ionization quadrupole mass spectrometry. J Am Soc Mass Spectrom 6:27-39.
95. Lin ZJ, Li W, Dai G. 2007. Application of LC-MS for quantitative analysis and metabolite identification of therapeutic oligonucleotides. J Pharm Biomed Anal 44:330-341.
96. Little DP, Jacob A, Becker T, Braun A, Darnhofer-Demar B, Jurinke C, van den Boom D, Koster H. 1997. Direct detection of synthetic and biologically generated double-stranded DNA by MALDI-TOF MS. Int J Mass Spectrom Ion Processes 169/170:323-330.
97. Liu C, Wu Q, Harms AC, Smith RD. 1996. On-line microdialysis sample cleanup for electrospray ionization mass spectrometry of nucleic acid samples. Anal Chem 68:3295-3299.
98. Liu C, Muddiman DC, Tang K, Smith RD. 1997. Improving the microdialysis procedure for electrospray ionization mass spectrometry of biological samples. J Mass Spectrom 32:425-431.
99. Loo JA. 1997. Studying noncovalent complexes by electrospray ionization mass spectrometry. Mass Spectrom Rev 16:1-23.
100. Mack GS. 2007. MicroRNA gets down to business. Nat Biotechnol 25:631-638.
101. MacRae IJ, Ma E, Zhou M, Robinson CV, Doudna JA. 2008. In vitro reconstitution of the human RISC-loading complex. Proc Natl Acad Sci USA 105:512-517.
102. Manoharan M. 2004. RNA interference and chemically modified small interfering RNAs. Curr Opin Chem Biol 8:570-579.
103. Maroney PA, Chamnongpol S, Souret F, Nilsen TW. 2007. A rapid, quantitative assay for direct detection of microRNAs and other small RNAs using splinted ligation. RNA 13:930-936.
104. McCarthy SM, Gilar M, Gebler J. 2009. Reversed-phase ion-pair liquid chromatography analysis and purification of small interfering RNA. Anal Biochem 390:181-188.
105. McCloskey JA, Whitehill AB, Rozenski J, Qui F, Crain PF. 1999. New techniques for the rapid characterization of oligonucleotides by mass spectrometry. Nucleosides Nucleotides 18:1549-1553.
106. McLuckey S, Van Berkel G, Glish G. 1992. Tandem mass spectrometry of small, multiply charged oligonucleotides. J Am Soc Mass Spectrom 3:60-70.
107. Meng Z, Limbach PA. 2006. Mass spectrometry ofRNA: Linking the genome to the proteome. Brief Funct Genomic Proteomic 5:87-95.
108. Mook OR, Baas F, de Wissel MB, Fluiter K. 2007. Evaluation of locked nucleic acid-modified small interfering RNA in vitro and in vivo. Mol Cancer Ther 6:833-843.
109. Morrissey DV, Blanchard K, Shaw L, Jensen K, Lockridge JA, Dickinson B, McSwiggen JA, Vargeese C, Bowman K, Shaffer CS, Polisky BA, Zinnen S. 2005a. Activity of stabilized short interfering RNA in a mouse model of hepatitis B virus replication. Hepatology 41:1349-1356.
110. Morrissey DV, Lockridge JA, Shaw L, Blanchard K, Jensen K, Breen W, Hartsough K, Machemer L, Radka S, Jadhav V, Vaish N, Zinnen S, Vargeese C, Bowman K, Shaffer CS, Jeffs LB, Judge A, MacLachlan I, Polisky B. 2005b. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat Biotechnol 23:1002-1007.
111. Muddiman DC, Cheng X, Udseth HR, Smith RD. 1996. Charge-state reduction with improved signal intensity of oligonucleotides in electrospray ionization mass spectrometry. J Am Soc Mass Spectrom 7:697-706.
112. Murphy AT, Brown-Augsburger P, Yu RZ, Geary RS, Thibodeaux S, Ackermann BL. 2005. Development of an ion-pair reverse-phase liquid chromatographic/tandem mass spectrometry method for the determination of an 18-mer phosphorothioate oligonucleotide in mouse liver tissue. Eur J Mass Spectrom (Chichester, Eng) 11:209-215.
113. Nordhoff E, Ingendoh A, Cramer R, Overberg A, Stahl B, Karas M, Hillenkamp F, Crain PF. 1992. Matrix-assisted laser desorption/ ionization mass spectrometry of nucleic acids with wavelengths in the ultraviolet and infrared. Rapid Commun Mass Spectrom 6:771-776.
114. Novina CD, Sharp PA. 2004. The RNAi revolution. Nature 430:161-164.
115. Null AP, Nepomuceno AI, Muddiman DC. 2003. Implications of hydrophobicity and free energy of solvation for characterization of nucleic acids by electrospray ionization mass spectrometry. Anal Chem 75: 1331-1339.
116. Oberacher H, Parson W, Oefner PJ, Mayr BM, Huber CG. 2004b. Applicability of tandem mass spectrometry to the automated comparative sequencing of long-chain oligonucleotides. J Am Soc Mass Spectrom 15:510-522.
117. Oberacher H, Premstaller A, Huber CG. 2004c. Characterization of some physical and chromatographic properties of monolithic poly(styreneco- divinylbenzene) columns. J Chromatogr A 1030:201-208.
118. Oberacher H, Niederstatter H, ParsonW. 2005. Characterization of synthetic nucleic acids by electrospray ionization quadrupole time-of-flight mass spectrometry. J Mass Spectrom 40:932-945.
119. Ohara T, SakaguchiY, Suzuki T, Ueda H, Miyauchi K. 2007. The 30 termini of mouse Piwi-interacting RNAs are 20-O-methylated. Nat Struct Mol Biol 14:349-350.
120. Ono T, Scalf M, Smith LM. 1997. 20-Fluoro modified nucleic acids: Polymerase-directed synthesis, properties and stability to analysis by matrix-assisted laser desorption/ionization mass spectrometry. Nucleic Acids Res 25:4581-4588.
121. Overhoff M,Wunsche W, Sczakiel G. 2004. Quantitative detection of siRNA and single-stranded oligonucleotides: Relationship between uptake and biological activity of siRNA. Nucleic Acids Res 32:e170.
122. Pan S, Sun X, Lee JK. 2006a. DNA stability in the gas versus solution phases: A systematic study of thirty-one duplexes with varying length, sequence, and charge level. J Am Soc Mass Spectrom 17:1383-1395.
123. Pan S, Sun X, Lee JK. 2006b. Stability of complementary and mismatched DNA duplexes: Comparison and contrast in gas versus solution phases. Int J Mass Spectrom 253:238-248.
124. Pieles U, Zürcher W, Schär M, Moser H. 1993. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry:Apowerful tool for the mass and sequence analysis of natural and modified oligonucleotides. Nucleic Acids Res 21:3191-3196.
125. Portmann S, Usman N, Egli M. 1995. The crystal structure of r(CCCCGGGG) in two distinct lattices. Biochemistry 34:7569-7575.
126. Premstaller A, Oberacher H, Huber CG. 2000. High-performance liquid chromatography-electrospray ionization mass spectrometry of singleand double-stranded nucleic acids using monolithic capillary columns. Anal Chem 72:4386-4393.
127. Qiu F, McCloskey JA. 1999. Selective detection of ribose-methylated nucleotides in RNA by a mass spectrometry-based method. Nucleic Acids Res 27:e20.
128. Rana TM. 2007. Illuminating the silence: Understanding the structure and function of small RNAs. Nat Rev Mol Cell Biol 8:23-36.
129. Ravikumar VT, Kumar RK, Capaldi DC, Cole DL. 2003. Synthesis of high quality phosphorothioate oligonucleotides as antisense drugs. Use of Ilinker in the elimination of 30-terminal phosphorothioate monoesters. Nucleosides Nucleotides Nucleic Acids 22:1421-1425.
130. Raymond CK, Roberts BS, Garrett-Engele P, Lim LP, Johnson JM. 2005. Simple, quantitative primer-extension PCR assay for direct monitoring of microRNAs and short-interfering RNAs. RNA 11:1737-1744.
131. Rentel C,Wang X, Batt M, Kurata C, Oliver J, Gaus H, Krotz AH, McArdle JV, Capaldi DC. 2005. Formation of modified cytosine residues in the presence of depurinated DNA. J Org Chem 70:7841-7845.
132. Rodrigues Hoyne P, Benson LM, Veenstra TD, Maher LJ, Naylor S III. 2001. RNA-RNA noncovalent interactions investigated by microspray ionization mass spectrometry. Rapid Commun Mass Spectrom 15: 1539-1547.
133. Rose SD, Kim DH, Amarzguioui M, Heidel JD, Collingwood MA,Davis ME, Rossi JJ, Behlke MA. 2005. Functional polarity is introduced by dicer processing of short substrate RNAs. Nucleic Acids Res 33:4140-4156.
134. Rusconi F, Guillonneau F, Praseuth D. 2002. Contributions of mass spectrometry in the study of nucleic acid-binding proteins and of nucleic acid-protein interactions. Mass Spectrom Rev 21:305-348.
135. Sannes-Lowery KA, Hofstadler SA. 2003. Sequence confirmation of modified oligonucleotides using IRMPD in the external ion reservoir of an electrospray ionization Fourier transform ion cyclotron mass spectrometer. J Am Soc Mass Spectrom 14:825-833.
136. Sannes-Lowery KA, Drader JJ, Griffey RH, Hofstadler SA. 2000. Fourier transform ion cyclotron resonance mass spectrometry as a high throughput affinity screen to identify RNA binding ligands. Trends Anal Chem 19:481-491.
137. Sauer S. 2007. The essence of DNA sample preparation for MALDI mass spectrometry. J Biochem Biophys Methods 70:311-318.
138. Schnier PD, Klassen JS, Strittmatter EF, Williams ER. 1998. Activation energies for dissociation of double strand oligonucleotide anions: Evidence for Watson-Crick base pairing in vacuo. JAmChem Soc 120: 9605-9613.
139. Shah S, Friedman SH. 2007. Tolerance of RNA interference toward modifications of the 50 antisense phosphate of small interfering RNA. Oligonucleotides 17:35-43.
140. Shah S, Friedman SH. 2008. An ESI-MS method for characterization of native and modified oligonucleotides used for RNA interference and other biological applications. Nat Protoc 3:351-356.
141. Shah S, Rangarajan S, Friedman SH. 2005. Light-activatedRNAinterference. Angew Chem Int Ed Engl 44:1328-1332.
142. Shi R, Chiang VL. 2005. Facile means for quantifying microRNA expression by real-time PCR. Biotechniques 39:519-525.
143. Stratford S, Stec S, Jadhav V, Seitzer J, Abrams M, Beverly M. 2008. Examination of real-time polymerase chain reaction methods for the detection and quantification of modified siRNA. Anal Biochem 379: 96-104.
144. Stults JT, Marsters JC. 1991. Improved electrospray ionization of synthetic oligodeoxynucleotides. Rapid Commun Mass Spectrom 5:359-363.
145. Sturm M, Quinten S, Huber CG, Kohlbacher O. 2007. A statistical learning approach to the modeling of chromatographic retention of oligonucleotides incorporating sequence and secondary structure data. Nucleic Acids Res 35:4195-4202.
146. Sudha R, Zenobi R. 2002. The detection and stability of DNA duplexes probed by MALDI mass spectrometry. Helv Chim Acta 85:3136-3143.
147. TangW, Krause J, Zhu L, Smith LM. 1997. Factors influencing oligonucleotide stability in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. Int J Mass Spectrom Ion Processes 169/170:301-311.
148. Thomas B, Akoulitchev AV. 2006. Mass spectrometry of RNA. Trends Biochem Sci 31:173-181.
149. Tromp JM, Schurch S. 2005. Gas-phase dissociation of oligoribonucleotides and their analogs studied by electrospray ionization tandem mass spectrometry. J Am Soc Mass Spectrom 16:1262-1268.
150. Turner JJ, Jones SW, Moschos SA, Lindsay MA, Gait MJ. 2007. MALDITOF mass spectral analysis of siRNA degradation in serum confirms an RNAse A-like activity. Mol Biosyst 3:43-50.
151. Varkonyi-Gasic E,Wu R,Wood M,Walton EF, Hellens RP. 2007. Protocol:A highly sensitive RT-PCR method for detection and quantification of microRNAs. Plant Methods 3:12.
152. Wang BH, Hopkins CE, Belenky AB, Cohen AS. 1997. Sequencing of modified oligonucleotides using in-source fragmentation and delayed pulsed ion extraction matrix-assisted laser desorption ionization timeof- flight mass spectrometry. Int J Mass Spectrom Ion Processes 169/ 170:3313-3350.
153. Wu R, Wood M, Thrush A, Walton EF, Varkonyi-Gasic E. 2007. Real-time PCR quantification of plant miRNAs using Universal ProbeLibrary Technology. Biochemica 2:12-15.
154. Xiang F, Lin Y, Wen J, Matson DW, Smith RD. 1999. An integrated microfabricated device for dual microdialysis and on-line ESI-ion trap mass spectrometry for analysis of complex biological samples. Anal Chem 71:1485-1490.
155. Yang M, Mattes J. 2008. Discovery, biology and therapeutic potential of RNA interference, microRNA and antagomirs. Pharmacol Ther 117:94-104.
156. Yang M, Thompson G, Hall J. 2004. Comparative stability determination of oligonucleotide duplexes in gas and solution phases. JAm Soc Mass Spectrom 15:1354-1359.
157. Yu RZ, Geary RS, Levin AA. 2004. Application of novel quantitative bioanalytical methods for pharmacokinetic and pharmacokinetic/ pharmacodynamic assessments of antisense oligonucleotides. Curr Opin Drug Discov Devel 7:195-203.
158. Yu B, Yang Z, Li J, Minakhina S, Yang M, Padgett RW, Steward R, Chen X. 2005. Methylation as a crucial step in plant microRNA biogenesis. Science 307:932-935.
159. Zamore PD. 2006. RNA interference: Big applause for silencing in Stockholm. Cell 127:1083-1086.
160. Zhang G, Lin J, Srinivasan K, Kavetskaia O, Duncan JN. 2007. Strategies for bioanalysis of an oligonucleotide class macromolecule from rat plasma using liquid chromatography-tandem mass spectrometry. Anal Chem 79:3416-3424.
161. Zou Y, Tiller P, Chen I-W, Beverly M, Hochman J. 2008. Metabolite identification of small interfering RNA duplex by high-resolution accurate mass spectrometry. Rapid Commun Mass Spectrom 22:1871-1881.