Methods of obtaining active antisense compounds

Freier, Susan M.; Matveeva, Olga; Tsodikov, Alexander; Giddings, Michael C.; Wyatt, Jacqueline R.

Methods of obtaining active antisense compounds

Patent · 22 September 2009

OSTI ID:1531599

Freier, Susan M.; Matveeva, Olga; Tsodikov, Alexander; Giddings, Michael C.; Wyatt, Jacqueline R.

Methods for obtaining antisense oligonucleotides with activity against a desired target are provided. Methods of identifying oligonucleotide sequence motifs which are predictive of antisense oligonucleotide activity are provided, as are motifs identified according to this method. Methods of selecting effective antisense oligonucleotide sequences and effective antisense target sequences are provided, as are sequences selected according to these methods. In other methods of the invention, oligonucleotides are designed to hybridize to target sequences containing one or more activity-enhancing motifs. Antisense oligonucleotides designed according to these methods are also provided.

Research Organization:: Isis Pharmaceuticals, Inc., Carlsbad, CA (United States); Univ. of Utah, Salt Lake City, UT (United States)

Sponsoring Organization:: USDOE

DOE Contract Number:: FG03-99ER62732

Assignee:: Isis Pharmaceuticals, Inc. (Carlsbad, CA); University of Utah Research Foundation (Salt Lake City, UT)

Patent Number(s):: 7,592,440

Application Number:: 10/686,317

OSTI ID:: 1531599

Country of Publication:: United States

Language:: English

References (9)

Predicting oligonucleotide affinity to nucleic acid targets Mathews, David H.; Burkard, Mark E.; Freier, Susan M. RNA, Vol. 5, Issue 11 https://doi.org/10.1017/S1355838299991148	journal	November 1999
Predicting antisense oligonucleotide inhibitory efficacy: a computational approach using histograms and thermodynamic indices Stull, Robert A.; Taylor, Leslie A.; Szoka, Francis C. Nucleic Acids Research, Vol. 20, Issue 13 https://doi.org/10.1093/nar/20.13.3501	journal	January 1992
Combinatorially selected guanosine-quartet structure is a potent inhibitor of human immunodeficiency virus envelope-mediated cell fusion. Wyatt, J. R.; Vickers, T. A.; Roberson, J. L. Proceedings of the National Academy of Sciences, Vol. 91, Issue 4 https://doi.org/10.1073/pnas.91.4.1356	journal	February 1994
A theoretical approach to select effective antisense oligodeoxyribonucleotides at high statistical probability Patzel, V.; Steidl, U.; Kronenwett, R. Nucleic Acids Research, Vol. 27, Issue 22 https://doi.org/10.1093/nar/27.22.4328	journal	November 1999
Tetranucleotide GGGA Motif in Primary RNA Transcripts: NOVEL TARGET SITE FOR ANTISENSE DESIGN Tu, Guang-chou; Cao, Qing-na; Zhou, Feng Journal of Biological Chemistry, Vol. 273, Issue 39 https://doi.org/10.1074/jbc.273.39.25125	journal	September 1998
Reduction of expression of the multidrug resistance protein (MRP) in human tumor cells by antisense phosphorothioate oligonucleotides Stewart, Alistair J.; Canitrot, Yvan; Baracchini, Edgardo Biochemical Pharmacology, Vol. 51, Issue 4 https://doi.org/10.1016/0006-2952(95)02220-1	journal	February 1996
Oligonucleotides Containing the G-Quartet Sequence Motif Wyatt, Jacqueline R.; Stein, C. A. Applications of Antisense Therapies to Restenosis https://doi.org/10.1007/978-1-4615-5183-6_8	book	January 1999
Kinetics of G-Quartet-Mediated Tetramer Formation Wyatt, Jacqueline R.; Davis, Peter W.; Freier, Susan M. Biochemistry, Vol. 35, Issue 24 https://doi.org/10.1021/bi960124h	journal	January 1996
Bias in Nucleotide Composition of Antisense Oligonucleotides Smetsers, Toon F. C. M.; Boezeman, Jan B. M.; Mensink, Ewald J. B. M. Antisense and Nucleic Acid Drug Development, Vol. 6, Issue 1 https://doi.org/10.1089/oli.1.1996.6.63	journal	January 1996

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