PMID: 8948649Nov 15, 1996Paper

Inhibition of the erbB-2 tyrosine kinase receptor in breast cancer cells by phosphoromonothioate and phosphorodithioate antisense oligonucleotides

Nucleic Acids Research
J P VaughnJ R Marks

Abstract

Antisense activity against erbB-2 of a variety of sulfur-modified oligonucleotides was examined in a breast cancer cell line which overexpresses this oncogene. Using a 15 base anti-erbB-2 sequence previously shown to be effective, various backbone configurations containing phosphoromonothioate or phosphorodithioate linkages were evaluated for antisense activity by a two-color flow cytometric assay. This sequence was effective in inhibiting the production of erbB-2 protein when it was configured as a monothioate at each linkage and as an alternating dithioate/phosphodiester. Both of these compounds were also able to specifically inhibit erbB-2 mRNA expression, indicative of RNase H-mediated activity. The same sequence protected by either three dithioate or three monothioate linkages at each end was ineffective as an antisense reagent, suggesting that endonuclease activity is a significant determinant of the stability of oligonucleotides. Finally, the erbB-2 sequence target was shifted in an effort to improve antisense activity. A new lead sequence was identified that was significantly more effective in inhibiting erbB-2 protein levels and retained activity at lower concentrations.

References

Apr 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·A M DavidoffJ R Marks
Jan 11, 1991·American Journal of Obstetrics and Gynecology·A BerchuckR C Bast
Feb 25, 1991·Nucleic Acids Research·J P ShawB Froehler
Apr 25, 1988·Nucleic Acids Research·C A SteinJ S Cohen
Jun 10, 1988·Nucleic Acids Research·B FroehlerM Matteucci
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·J P VaughnJ R Marks
Jul 2, 1996·Biochemistry·L CumminsM H Caruthers

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Citations

Jul 11, 2003·Nucleic Acids Research·David SheehanDouglas J Dellinger
Oct 6, 1998·Annual Review of Biochemistry·S Verma, F Eckstein
Feb 17, 2001·The Journal of Investigative Dermatology·L AurelianJ W Burnett
Oct 1, 2013·Nuclear Medicine and Biology·Bishnuhari PaudyalEric Wickstrom
Oct 21, 2003·Nucleosides, Nucleotides & Nucleic Acids·Xin WangBarbara Ramsay Shaw
Sep 2, 2016·Current Protocols in Nucleic Acid Chemistry·Xianbin Yang
Dec 18, 2013·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Bob OlssonKaj Blennow
Jan 17, 2016·British Journal of Haematology·Kirsten Bleckmann, Martin Schrappe
Jun 6, 2002·Journal of the American Chemical Society·Kenneth E JenkinsMarvin H Caruthers
Jan 23, 2003·Journal of the American Chemical Society·Douglas J DellingerMarvin H Caruthers

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