RNA interference for performance enhancement and detection in doping control

Drug Testing and Analysis

Volumn 3, Issue 10, 2011, Pages 661-667

  Kohler, Maxie ^a   Schänzer, Wilhelm ^a   Thevis, Mario ^a  

^a GERMAN SPORT UNIVERSITY COLOGNE   (Germany)

Author keywords

Antisense oligonucleotide; Clinical study; Doping; Gene doping; Mass spectrometry; MiRNA; SiRNA; Sport

Indexed keywords

DISEASES; GENE EXPRESSION; METABOLISM; OLIGONUCLEOTIDES; PHYSIOLOGY; PROTEINS; RNA; SPORTS;

ANTISENSE OLIGONUCLEOTIDES; CLINICAL STUDY; DOPING CONTROL; DOWN-REGULATION; GENE DOPING; GENES EXPRESSION; MIRNA; PERFORMANCE ENHANCEMENTS; RNA INTERFERENCE; SIRNA;

MASS SPECTROMETRY;

ANTISENSE OLIGONUCLEOTIDE; MICRORNA; SMALL INTERFERING RNA;

ANTISENSE THERAPY; CELL TRANSFER; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG STABILITY; DRUG STRUCTURE; GENE CONTROL; GENE EXPRESSION REGULATION; HUMAN; MASS SPECTROMETRY; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROCESSING; RNA INTERFERENCE; SHORT SURVEY; SIGNAL TRANSDUCTION; ANIMAL; DOPING; GENETICS; METHODOLOGY; REVIEW;

ANIMALS; DOPING IN SPORTS; HUMANS; MASS SPECTROMETRY; OLIGONUCLEOTIDES, ANTISENSE; RNA INTERFERENCE; RNA, SMALL INTERFERING;

EID: 84857079032     PISSN: 19427603     EISSN: 19427611     Source Type: Journal    
DOI: 10.1002/dta.330     Document Type: Short Survey

References (44)

1. WADA. The 2011 Prohibited List. Available at: [10 April 2011].
2. J. Kurreck RNA interference: from basic research to therapeutic applications. Angew. Chem. Int. Ed. Engl. 2009, 48, 1378.
3. J. Krutzfeldt, N. Rajewsky, R. Braich, K.G. Rajeev, T. Tuschl, M. Manoharan, M. Stoffel Silencing of microRNAs in vivo with 'antagomirs'. Nature 2005, 438, 685.
4. J. Kurreck Antisense technologies. Improvement through novel chemical modifications. Eur. J. Biochem. 2003, 270, 1628.
5. C. M. Liu, Z. Yang, C. W. Liu, R. Wang, P. Tien, R. Dale, L. Q. Sun Myostatin antisense RNA-mediated muscle growth in normal and cancer cachexia mice. Gene Ther. 2008, 15, 155.
6. M. G. Dunckley, M. Manoharan, P. Villiet, I. C. Eperon, G. Dickson Modification of splicing in the dystrophin gene in cultured Mdx muscle cells by antisense oligoribonucleotides. Hum. Mol. Genet. 1998, 7, 1083.
7. S. P. Walton, M. Wu, J. A. Gredell, C. Chan Designing highly active siRNAs for therapeutic applications. FEBS J. 2010, 277, 4806.
8. A. Reynolds, D. Leake, Q. Boese, S. Scaringe, W. S. Marshall, A. Khvorova Rational siRNA design for RNA interference. Nat. Biotechnol. 2004, 22, 326.
9. I. S. Cho, J. Kim, H. Lim do, H. C. Ahn, H. Kim, K. B. Lee, Y. S. Lee Improved serum stability and biophysical properties of siRNAs following chemical modifications. Biotechnol. Lett. 2008, 30, 1901.
10. J. B. Bramsen, M. B. Laursen, A. F. Nielsen, T. B. Hansen, C. Bus, N. Langkjaer, B. R. Babu, T. Hojland, M. Abramov, A. Van Aerschot, D. Odadzic, R. Smicius, J. Haas, C. Andree, J. Barman, M. Wenska, P. Srivastava, C. Zhou, D. Honcharenko, S. Hess, E. Muller, G. V. Bobkov, S. N. Mikhailov, E. Fava, T. F. Meyer, J. Chattopadhyaya, M. Zerial, J. W. Engels, P. Herdewijn, J. Wengel, J. Kjems A large-scale chemical modification screen identifies design rules to generate siRNAs with high activity, high stability and low toxicity. Nucl. Acids Res. 2009, 37, 2867.
11. D. R. Corey Chemical modification: the key to clinical application of RNA interference? J. Clin. Invest. 2007, 117, 3615.
12. R. Juliano, J. Bauman, H. Kang, X. Ming Biological barriers to therapy with antisense and siRNA oligonucleotides. Mol. Pharm. 2009, 6, 686.
13. S. Kawakami, M. Hashida Targeted delivery systems of small interfering RNA by systemic administration. Drug Metab. Pharmacokinet. 2007, 22, 142.
14. U. S. I. o. Health. Available at: [12 March 2011].
15. L.R. Grillone, R. Lanz Fomivirsen. Drugs Today (Barc) 2001, 37, 245.
16. M. Bozza, R. D. Sheardy, E. Dilone, S. Scypinski, M. Galazka Characterization of the secondary structure and stability of an RNA aptamer that binds vascular endothelial growth factor. Biochemistry 2006, 45, 7639.
17. E. S. Gragoudas, A. P. Adamis, E. T. Cunningham Jr., M. Feinsod, D. R. Guyer Pegaptanib for neovascular age-related macular degeneration. New Engl. J. Med. 2004, 351, 2805.
18. C. Konrad, G. Schupfer, M. Wietlisbach, H. Gerber Insulin as an anabolic: hypoglycemia in the bodybuilding world. Anasthesiol. Intensivmed. Notfallmed. Schmerzther. 1998, 33, 461.
19. B. C. Melnik Androgen abuse in the community. Curr. Opin. Endocrinol. Diabetes Obes. 2009, 16, 218.
20. M. Thevis, A. Thomas, W. Schänzer Mass spectrometric determination of insulins and their degradation products in sports drug testing. Mass Spectrom. Rev. 2008, 27, 35.
21. T. K. Lund Asthma in elite athletes: how do we manage asthma-like symptoms and asthma in elite athletes? Clin. Respir. J. 2009, 3, 123.
22. G. M. Gauvreau, L. P. Boulet, D. W. Cockcroft, A. Baatjes, J. Cote, F. Deschesnes, B. Davis, T. Strinich, K. Howie, M. Duong, R. M. Watson, P. M. Renzi, P. M. O'Byrne Antisense therapy against CCR3 and the common beta chain attenuates allergen-induced eosinophilic responses. Am. J. Respir. Crit. Care Med. 2008, 177, 952.
23. B. M. Pluim, O. de Hon, J. B. Staal, J. Limpens, H. Kuipers, S. E. Overbeek, A. H. Zwinderman, R. J. Scholten Beta-Agonists and physical performance: a systematic review and meta-analysis of randomized controlled trials. Sports Med. 2011, 41, 39.
24. J. C. van Deutekom, A. A. Janson, I. B. Ginjaar, W. S. Frankhuizen, A. Aartsma-Rus, M. Bremmer-Bout, J. T. den Dunnen, K. Koop, A. J. van der Kooi, N. M. Goemans, S. J. de Kimpe, P. F. Ekhart, E. H. Venneker, G. J. Platenburg, J. J. Verschuuren, G. J. van Ommen Local dystrophin restoration with antisense oligonucleotide PRO051. New Engl. J. Med. 2007, 357, 2677.
25. M. Kinali, V. Arechavala-Gomeza, L. Feng, S. Cirak, D. Hunt, C. Adkin, M. Guglieri, E. Ashton, S. Abbs, P. Nihoyannopoulos, M. E. Garralda, M. Rutherford, C. McCulley, L. Popplewell, I. R. Graham, G. Dickson, M. J. Wood, D. J. Wells, S. D. Wilton, R. Kole, V. Straub, K. Bushby, C. Sewry, J. E. Morgan, F. Muntoni Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study. Lancet Neurol. 2009, 8, 918.
26. M. Schuelke, K. R. Wagner, L. E. Stolz, C. Hubner, T. Riebel, W. Komen, T. Braun, J. F. Tobin, S. J. Lee Myostatin mutation associated with gross muscle hypertrophy in a child. New Engl. J. Med. 2004, 350, 2682.
27. D. S. Mosher, P. Quignon, C. D. Bustamante, N. B. Sutter, C. S. Mellersh, H. G. Parker, E. A. Ostrander A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs. PLoS Genet. 2007, 3, e79.
28. J. K. Kang, A. Malerba, L. Popplewell, K. Foster, G. Dickson Antisense-induced myostatin exon skipping leads to muscle hypertrophy in mice following octa-guanidine morpholino oligomer treatment. Mol. Ther. 2011, 19, 159.
29. J. Krutzfeldt, S. Kuwajima, R. Braich, K. G. Rajeev, J. Pena, T. Tuschl, M. Manoharan, M. Stoffel Specificity, duplex degradation and subcellular localization of antagomirs. Nucleic. Acids Res. 2007, 35, 2885.
30. C. Esau, S. Davis, S. F. Murray, X. X. Yu, S. K. Pandey, M. Pear, L. Watts, S. L. Booten, M. Graham, R. McKay, A. Subramaniam, S. Propp, B. A. Lollo, S. Freier, C. F. Bennett, S. Bhanot, B. P. Monia miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell. Metab. 2006, 3, 87.
31. S. Gao, F. Dagnaes-Hansen, E. J. Nielsen, J. Wengel, F. Besenbacher, K. A. Howard, J. Kjems The effect of chemical modification and nanoparticle formulation on stability and biodistribution of siRNA in mice. Mol. Ther. 2009, 17, 1225.
32. 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, H. P. Vornlocher Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 2004, 432, 173.
33. R. Z. Yu, T. W. Kim, A. Hong, T. A. Watanabe, H. J. Gaus, R. S. Geary Cross-species pharmacokinetic comparison from mouse to man of a second-generation antisense oligonucleotide, ISIS 301012, targeting human apolipoprotein B-100. Drug Metab. Dispos. 2007, 35, 460.
34. T. Miyao, Y. Takakura, T. Akiyama, F. Yoneda, H. Sezaki, M. Hashida Stability and pharmacokinetic characteristics of oligonucleotides modified at terminal linkages in mice. Antisense. Res. Dev. 1995, 5, 115.
35. G. Zhang, J. Lin, K. Srinivasan, O. Kavetskaia, J. N. Duncan Strategies for bioanalysis of an oligonucleotide class macromolecule from rat plasma using liquid chromatography-tandem mass spectrometry. Anal. Chem. 2007, 79, 3416.
36. I. G. Shishkina, F. Johnson A new method for the postsynthetic generation of abasic sites in oligomeric DNA. Chem. Res. Toxicol. 2000, 13, 907.
37. M. Greig, R. H. Griffey Utility of organic bases for improved electrospray mass spectrometry of oligonucleotides. Rapid Commun. Mass Spectrom. 1995, 9, 97.
38. M. Kohler, A. Thomas, K. Walpurgis, W. Schänzer, M. Thevis The use of siRNA as performance enhancing agent and detection in doping control. Presentation at the 28th Cologne Workshop on Dope Analysis, Cologne, Germany, 2010, March 7-12, 2010.
39. Y. Zou, P. Tiller, I. W. Chen, M. Beverly, J. Hochman Metabolite identification of small interfering RNA duplex by high-resolution accurate mass spectrometry. Rapid Commun. Mass Spectrom. 2008, 22, 1871.
40. T. Y. Huang, J. Liu, X. Liang, B. D. Hodges, S. A. McLuckey Collision-induced dissociation of intact duplex and single-stranded siRNA anions. Anal. Chem. 2008, 80, 8501.
41. U. Bahr, H. Aygun, M. Karas Sequencing of single and double stranded RNA oligonucleotides by acid hydrolysis and MALDI mass spectrometry. Anal. Chem. 2009, 81, 3173.
42. C. G. Huber, H. Oberacher Analysis of nucleic acids by on-line liquid chromatography-mass spectrometry. Mass Spectrom. Rev. 2001, 20, 310.
43. M. Beverly, K. Hartsough, L. Machemer Liquid chromatography/electrospray mass spectrometric analysis of metabolites from an inhibitory RNA duplex. Rapid Commun. Mass Spectrom. 2005, 19, 1675.
44. M. Kohler, A. Thomas, K. Walpurgis, W. Schänzer, M. Thevis Mass spectrometric detection of siRNA in plasma samples for doping control purposes. Anal. Bioanal. Chem. 2010, 398, 1305.