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Title:
METHOD FOR DESIGNING SMALL RNA DUPLEX AND HAIRPIN RNA
Document Type and Number:
WIPO Patent Application WO/2011/001965
Kind Code:
A1
Abstract:
Provided is a method for designing a small RNA duplex or a hairpin RNA that has a high knockdown efficiency in not only in tissue with a high expression of Ago2 (the heart, kidneys, etc. in humans), but also in tissue with a low expression of Ago2 (the liver, pancreas, etc. in humans). The method for designing a small RNA duplex or a hairpin RNA involves designing the sequence of the strand that is integrated into an RISC complex (a guide strand) so as to increase the complementarity with a target mRNA sequence in the complimentary duplex portion of the small RNA duplex or the hairpin RNA; and involves, in regards to the sequence of the strand that is degraded from the RISC complex (a passenger strand), (1) performing at least one base substitution in the position on the passenger strand corresponding to the center of the guide strand (positions 9-11 from the 5' end) and introducing a mismatch or a G:U wobble pair, and (2) performing at least one base substitution in the position on the passenger strand corresponding to the seed region of the guide strand (positions 2-8 from the 5' end) and/or the 3'-mid region of the guide strand (positions 12-16 from the 5' end) and introducing a mismatch or a G:U wobble pair, using a sequence that is complimentary to the guide strand as a standard.

Inventors:
TOMARI YUKIHIDE (JP)
KAWAMATA TOMOKO (JP)
YODA MAYUKO (JP)
Application Number:
PCT/JP2010/061036
Publication Date:
January 06, 2011
Filing Date:
June 29, 2010
Export Citation:
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Assignee:
UNIV TOKYO (JP)
TOMARI YUKIHIDE (JP)
KAWAMATA TOMOKO (JP)
YODA MAYUKO (JP)
International Classes:
C12N15/09; C12N5/10
Domestic Patent References:
WO2008147839A12008-12-04
Other References:
HU, ZHIBIN ET AL.: "Genetic variants of miRNA sequences and non-small cell lung cancer survival.", J. CLINICAL INVESTIGATION, vol. 118, no. 7, 2008, pages 2600 - 2608
YEKTA, S. ET AL.: "MicroRNA-directed cleavage of HOXB8 mRNA.", SCIENCE, vol. 304, no. 5670, 2004, pages 594 - 596, XP003034012, DOI: doi:10.1126/science.1097434
BRODERSEN, P. ET AL.: "Revisiting the principles of microRNA target recognition and mode of action.", NATURE REVIEWS MOLECULAR CELL BIOLOGY, vol. 10, no. 2, February 2009 (2009-02-01), pages 141 - 148
KAWAMATA, T. ET AL.: "Structural determinants of miRNAs for RISC loading and slicer-independent unwinding.", NATURE STRUCTRAL & MOLECULAR BIOLOGY, vol. 16, no. 9, 16 August 2009 (2009-08-16), pages 953 - 960
KAWAMATA, T ET AL.: "Making RISC", TRENDS IN BIOCHEMICAL SCIENCES, vol. 35, 13 April 2010 (2010-04-13), pages 368 - 376, XP027117665
Attorney, Agent or Firm:
SIKs & Co. (JP)
Patent business corporation patent firm Sykes (JP)
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