Mapping of RNA accessible sites for antisense experiments with oligonucleotide libraries

Nature Biotechnology
S P HoR R Sakai

Abstract

Antisense experiments are often complicated by the lack of reliable methods for selecting effective antisense sequences. Chimeric oligodeoxynucleotide (ODN) libraries and ribonuclease H (RNase H) were used to identify regions on the 1253 nucleotide angiotensin type-1 receptor (AT1) mRNA that are accessible to hybridization with antisense ODNs. Phosphorothioate antisense ODNs targeted against accessible sites reduced AT1 receptor levels by at least 50% in cell culture. ODNs to 4 sites produced a 70% to 80% reduction. In contrast, most sequences targeted between accessible sites were ineffective. When injected into the brains of rats, ODNs targeted to accessible sites reduced AT1 (by 65%) but not AT2 receptor levels. Additionally, AT1 receptor function as measured by agonist-induced water intake, was significantly attenuated in these rats. ODNs directed between accessible sites were ineffective at suppressing water intake. RNA mapping can be applied to any RNA target to facilitate selection of multiple, active antisense sequences for cell culture and in vivo experiments.

References

Jan 1, 1987·Nucleic Acids Symposium Series·H InoueE Ohtsuka
Jan 1, 1995·Molecular and Cellular Biology·A Lieber, M Strauss
Apr 16, 1996·Proceedings of the National Academy of Sciences of the United States of America·A M GewirtzP M Glazer
Jul 18, 1997·The Journal of Biological Chemistry·W F LimaS T Crooke

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Citations

Feb 6, 2010·Applied Microbiology and Biotechnology·Masashi HatamotoHiroyuki Imachi
May 12, 2011·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·YaoFei WangChangYe Zou
Jun 1, 2001·Journal of Biochemical and Biophysical Methods·E ZamaratskiJ Chattopadhyaya
Aug 22, 2001·Biochimica Et Biophysica Acta·A JayaramanC M Roth
May 12, 2000·Biochimica Et Biophysica Acta·N Agarwal, A M Gewirtz
May 12, 2000·Biochimica Et Biophysica Acta·J Summerton
Apr 20, 2001·Brain Research. Molecular Brain Research·S P HoS P Arneric
Oct 18, 2000·Advanced Drug Delivery Reviews·M Sohail, E M Southern
Oct 24, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·L SmithJ W Jaroszewski
Oct 29, 2003·Current Opinion in Biotechnology·Li Kim Lee, Charles M Roth
Mar 21, 2001·Drug Discovery Today·M D. HughesS Akhtar
Dec 12, 2001·Drug Discovery Today·Muhammad Sohail
Nov 9, 2002·The Lancet Oncology·Burkhard Jansen, Uwe Zangemeister-Wittke
May 21, 2005·Nature Reviews. Cancer·Martin E Gleave, Brett P Monia
Feb 12, 2008·Proceedings of the National Academy of Sciences of the United States of America·Eirik W LundbladSidney Altman
Aug 7, 2002·Antisense & Nucleic Acid Drug Development·Richard J KlasaStanley R Frankel
Apr 15, 2003·Antisense & Nucleic Acid Drug Development·Emily L DeerJ Stephen Lodmell
Oct 6, 2005·Oligonucleotides·Rosel Kretschmer-Kazemi FarGeorg Sczakiel
Jul 20, 2007·Oligonucleotides·Sumiti Vinayak, Yagya D Sharma
Nov 25, 1998·Nucleic Acids Research·N K VaishF Eckstein
May 9, 2001·Nucleic Acids Research·A A MirP Hendry
Jul 15, 2009·Nucleic Acids Research·Andrew D KauffmannJessica L Childs-Disney

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