WO2008109548A3 - Nucleic acid compounds for inhibiting tgfb gene expression and uses thereof - Google Patents

Nucleic acid compounds for inhibiting tgfb gene expression and uses thereof Download PDF

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Publication number
WO2008109548A3
WO2008109548A3 PCT/US2008/055698 US2008055698W WO2008109548A3 WO 2008109548 A3 WO2008109548 A3 WO 2008109548A3 US 2008055698 W US2008055698 W US 2008055698W WO 2008109548 A3 WO2008109548 A3 WO 2008109548A3
Authority
WO
WIPO (PCT)
Prior art keywords
tgfb2
tgfb3
nucleic acid
gene expression
tgfbl
Prior art date
Application number
PCT/US2008/055698
Other languages
French (fr)
Other versions
WO2008109548A4 (en
WO2008109548A2 (en
Inventor
Steven C Quay
James Mcswiggen
Narendra K Vaish
Mohammad Ahmadian
Original Assignee
Mdrna Inc
Steven C Quay
James Mcswiggen
Narendra K Vaish
Mohammad Ahmadian
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Mdrna Inc, Steven C Quay, James Mcswiggen, Narendra K Vaish, Mohammad Ahmadian filed Critical Mdrna Inc
Publication of WO2008109548A2 publication Critical patent/WO2008109548A2/en
Publication of WO2008109548A3 publication Critical patent/WO2008109548A3/en
Publication of WO2008109548A4 publication Critical patent/WO2008109548A4/en
Priority to US12/552,082 priority Critical patent/US20100105134A1/en
Priority to US13/327,545 priority patent/US20130011922A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1136—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against growth factors, growth regulators, cytokines, lymphokines or hormones
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA

Abstract

The present disclosure provides meroduplex ribonucleic acid molecules (mdRNA) capable of decreasing or silencing TGFBl, TGFB2, and/or TGFB3 gene expression. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-overlapping double-stranded regions separated by a nick or gap wherein one strand is complementary to a TGFBl, TGFB2, and/or TGFB3 mRNA. In addition, the meroduplex may have at least one uridine is a 5-methyluridine, a nucleoside is a locked nucleic acid, or optionally other modifications, and any combination thereof. Also provided are methods of decreasing expression of a TGFB l, TGFB2, or TGFB3 gene in a cell or in a subject to treat a TGFBl-, TGFB2-, or TGFB3-related disease.
PCT/US2008/055698 2007-03-02 2008-03-03 Nucleic acid compounds for inhibiting tgfb gene expression and uses thereof WO2008109548A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US12/552,082 US20100105134A1 (en) 2007-03-02 2009-09-01 Nucleic acid compounds for inhibiting gene expression and uses thereof
US13/327,545 US20130011922A1 (en) 2007-03-02 2011-12-15 Nucleic acid compounds for inhibiting gene expression and uses thereof

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US93494007P 2007-03-02 2007-03-02
US60/934,940 2007-03-02
US93493007P 2007-03-16 2007-03-16
US60/934,930 2007-03-16
US1240207P 2007-12-07 2007-12-07
US61/012,402 2007-12-07

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/055695 Continuation-In-Part WO2008109546A2 (en) 2007-03-02 2008-03-03 Nucleic acid compounds for inhibiting tgfbr gene expression and uses thereof

Related Child Applications (3)

Application Number Title Priority Date Filing Date
PCT/US2008/055560 Continuation-In-Part WO2008109474A1 (en) 2007-03-02 2008-02-29 Nucleic acid compounds for inhibiting fgf2 gene expression and uses thereof
AU2009212920A Division AU2009212920A1 (en) 2007-03-02 2009-09-01 Nucleic acid compounds for inhibiting gene expression and uses thereof
US12/552,082 Continuation-In-Part US20100105134A1 (en) 2007-03-02 2009-09-01 Nucleic acid compounds for inhibiting gene expression and uses thereof

Publications (3)

Publication Number Publication Date
WO2008109548A2 WO2008109548A2 (en) 2008-09-12
WO2008109548A3 true WO2008109548A3 (en) 2009-02-26
WO2008109548A4 WO2008109548A4 (en) 2009-04-16

Family

ID=39739057

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/055698 WO2008109548A2 (en) 2007-03-02 2008-03-03 Nucleic acid compounds for inhibiting tgfb gene expression and uses thereof

Country Status (1)

Country Link
WO (1) WO2008109548A2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008049078A1 (en) 2006-10-18 2008-04-24 Nastech Pharmaceutical Company Inc. Nicked or gapped nucleic acid molecules and uses thereof
US20110172296A1 (en) * 2010-01-12 2011-07-14 Bennett C Frank Modulation of transforming growth factor-beta 1 expression
AR083445A1 (en) 2010-10-14 2013-02-27 Univ Mie siRNA AGAINST FIBROSIS
US10337009B2 (en) 2014-12-15 2019-07-02 Bonac Corporation Single-stranded nucleic acid molecule for inhibiting TGF-β1 expression

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004032855A2 (en) * 2002-10-07 2004-04-22 Isis Pharmaceuticals, Inc. Method for inhibiting angiogenesis with transforming growth factor-beta 3 inhibitors
WO2007056153A2 (en) * 2005-11-04 2007-05-18 Nastech Pharmaceutical Company Inc. Peptide-dicer substrate rna conjugates as delivery vehicles for sirna
WO2007107162A2 (en) * 2006-03-23 2007-09-27 Santaris Pharma A/S Small internally segmented interfering rna
WO2008049078A1 (en) * 2006-10-18 2008-04-24 Nastech Pharmaceutical Company Inc. Nicked or gapped nucleic acid molecules and uses thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004032855A2 (en) * 2002-10-07 2004-04-22 Isis Pharmaceuticals, Inc. Method for inhibiting angiogenesis with transforming growth factor-beta 3 inhibitors
WO2007056153A2 (en) * 2005-11-04 2007-05-18 Nastech Pharmaceutical Company Inc. Peptide-dicer substrate rna conjugates as delivery vehicles for sirna
WO2007107162A2 (en) * 2006-03-23 2007-09-27 Santaris Pharma A/S Small internally segmented interfering rna
WO2008049078A1 (en) * 2006-10-18 2008-04-24 Nastech Pharmaceutical Company Inc. Nicked or gapped nucleic acid molecules and uses thereof

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
BRAMSEN JESPER B. ET AL.: "Improved silencing properties using small internally segmented interfering RNAs", NUCLEIC ACIDS RESEARCH, OXFORD UNIVERSITY PRESS, SURREY, GB, vol. 35, no. 17, 28 July 2007 (2007-07-28), pages 5886 - 5897, XP002458184, ISSN: 0305-1048 *
CANIGGIA I ET AL.: "Inhibition of TGF-beta2 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnancies", JOURNAL OF CLINICAL INVESTIGATION, AMERICAN SOCIETY FOR CLINICAL INVESTIGATION, US, vol. 103, no. 12, 1 June 1999 (1999-06-01), pages 1641 - 1650, XP002961279, ISSN: 0021-9738 *
CANIGGIA I. ET AL.: "Oxygen and placental development during the first trimester: implications for the pathophysilogy of pre-eclampsia", PLACENTA, vol. 21, no. suppl.A, 2000, pages S25 - S30, XP009015478 *
FRIESE M.A. ET AL.: "RNA interference targeting Transforming Growth Factor-beta enhances NKG2D-mediated antiglioma immune response, inhibits glioma cell migration and invasiveness, and abrogates tumorigenicity in vivo", CANCER RESEARCH, vol. 64, 15 October 2004 (2004-10-15), pages 7596 - 7603, XP002504695 *
FUYOU LIU ET AL.: "Inhibition of TGF-beta1 expression in human peritoneal mesothelial cells by pcDU6 vector-mediated TGF-beta1 shRNA", NEPHROLOGY, vol. 11, 2006, pages 23 - 28, XP002504693 *
HAGERMAN K.R. AND HAGERMAN P.J.: "Helix rigidity of DNA: the meroduplex as an experimental paradigm", JOURNAL OF MOLECULAR BIOLOGY, vol. 260, 1996, pages 207 - 223, XP002484999 *
LEUSCHNER P J F ET AL: "Cleavage of the siRNA passenger strand during RISC assembly in human cells", EMBO REPORTS, vol. 7, no. 3, 1 March 2006 (2006-03-01), pages 314 - 320, XP002467845 *
LU TAO ET AL.: "Secreted transforming growth factor beta2 activates NF-kappaB, blocks apoptosis, and is essential for the survival of some tumor cells", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE, WASHINGTON, DC.; US, vol. 101, no. 18, 4 May 2004 (2004-05-04), pages 7112 - 7117, XP002347905, ISSN: 0027-8424 *
MATSUO S.E. ET AL.: "Transforming growth factor-beta1 and activin A generate antiproliferative signaling in thyroid cancer cells", JOURNAL OF ENDOCRINOLOGY, vol. 190, 2006, pages 141 - 150, XP002504694 *
MILLS JANINE B. ET AL.: "Origin of the intrinsic rigidity of DNA", NUCLEIC ACIDS RESEARCH,, vol. 32, no. 13, 1 January 2004 (2004-01-01), pages 4055 - 4059, XP002484664 *

Also Published As

Publication number Publication date
WO2008109548A4 (en) 2009-04-16
WO2008109548A2 (en) 2008-09-12

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