WO2011114106A3 - Gene silencing - Google Patents

Gene silencing Download PDF

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Publication number
WO2011114106A3
WO2011114106A3 PCT/GB2011/000378 GB2011000378W WO2011114106A3 WO 2011114106 A3 WO2011114106 A3 WO 2011114106A3 GB 2011000378 W GB2011000378 W GB 2011000378W WO 2011114106 A3 WO2011114106 A3 WO 2011114106A3
Authority
WO
WIPO (PCT)
Prior art keywords
sequence
mirtron
gene silencing
gene
splice site
Prior art date
Application number
PCT/GB2011/000378
Other languages
French (fr)
Other versions
WO2011114106A2 (en
Inventor
Matthew Wood
Christopher Sibley
Original Assignee
Isis Innovation Limited
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 Isis Innovation Limited filed Critical Isis Innovation Limited
Publication of WO2011114106A2 publication Critical patent/WO2011114106A2/en
Publication of WO2011114106A3 publication Critical patent/WO2011114106A3/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
    • C12N15/1137—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 enzymes
    • 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.
    • C12N2310/141—MicroRNAs, miRNAs
    • 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
    • C12N2310/50—Physical structure
    • C12N2310/53—Physical structure partially self-complementary or closed
    • C12N2310/533—Physical structure partially self-complementary or closed having a mismatch or nick in at least one of the strands

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Virology (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention provides a mirtron capable of reducing the expression of the LRRK2 gene in a mammalian cell, the sequence of the mirtron comprising: (i) a 5' splice site; (ii) a 3' splice site; (iii) a branch-point recognition sequence; (iv) a 3' polypyrimidine tract greater than 15 nucleotides in length; and (v) an antisense sequence that is at least partially complementary to a sequence in the LRRK2 mRNA, or a gene capable of expressing said mirtron.
PCT/GB2011/000378 2010-03-17 2011-03-17 Gene silencing WO2011114106A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB1004475.8 2010-03-17
GBGB1004475.8A GB201004475D0 (en) 2010-03-17 2010-03-17 Gene silencing

Publications (2)

Publication Number Publication Date
WO2011114106A2 WO2011114106A2 (en) 2011-09-22
WO2011114106A3 true WO2011114106A3 (en) 2012-01-05

Family

ID=42227891

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2011/000378 WO2011114106A2 (en) 2010-03-17 2011-03-17 Gene silencing

Country Status (2)

Country Link
GB (1) GB201004475D0 (en)
WO (1) WO2011114106A2 (en)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20170002350A1 (en) * 2013-12-03 2017-01-05 Agency For Science, Technology And Research Tailed mirtron effectors for rnai-mediated gene silencing
EP4008780A1 (en) * 2015-04-30 2022-06-08 The Trustees of Columbia University in the City of New York Gene therapy for autosomal dominant diseases
EP3377629B1 (en) 2015-11-18 2023-07-05 Rosalind Franklin University of Medicine and Science Antisense compounds targeting leucine-rich repeat kinase 2 (lrrk2) for the treatment of parkinsons disease
US10370667B2 (en) 2015-11-18 2019-08-06 Rosalind Franklin University Of Medicine And Science Antisense compounds targeting leucine-rich repeat kinase 2 (LRRK2) for the treatment of parkinsons disease
WO2017120365A1 (en) 2016-01-05 2017-07-13 Ionis Pharmaceuticals, Inc. Methods for reducing lrrk2 expression
KR101956315B1 (en) * 2017-07-19 2019-03-08 국민대학교 산학협력단 miR494 as a biomarker for parkinson’s disease and diagnostic kit using thereof
TWI833770B (en) 2018-06-27 2024-03-01 美商Ionis製藥公司 Compounds and methods for reducing lrrk2 expression
GB201817470D0 (en) * 2018-10-26 2018-12-12 Univ Oxford Innovation Ltd Gene therapy
AU2021211723A1 (en) * 2020-01-24 2022-08-04 Alnylam Pharmaceuticals, Inc. Leucine-rich repeat kinase 2 (LRRK2) iRNA agent compositions and methods of use thereof
CN113999847A (en) * 2021-10-11 2022-02-01 中山大学附属第六医院 sgRNA of specific target LRRK2 gene, lentivirus transfection vector and application thereof
WO2023194586A2 (en) * 2022-04-08 2023-10-12 Secarna Pharmaceuticals Gmbh & Co. Kg Oligonucleotide for reducing the expression of leucine-rich repeat kinase 2 (lrrk2) and its use for preventing and/or treating human diseases

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060171935A1 (en) * 2005-01-31 2006-08-03 Asa Abeliovich Protecting cell therapy for neurological disorders including Parkinson's disease

Family Cites Families (10)

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US5168062A (en) 1985-01-30 1992-12-01 University Of Iowa Research Foundation Transfer vectors and microorganisms containing human cytomegalovirus immediate-early promoter-regulatory DNA sequence
ES2116269T3 (en) 1989-03-21 1998-07-16 Vical Inc EXPRESSION OF EXOGENOUS SEQUENCES OF POLYNUCLEOTIDES IN A VERTEBRATE.
US5703055A (en) 1989-03-21 1997-12-30 Wisconsin Alumni Research Foundation Generation of antibodies through lipid mediated DNA delivery
US5399346A (en) 1989-06-14 1995-03-21 The United States Of America As Represented By The Department Of Health And Human Services Gene therapy
US5279833A (en) 1990-04-04 1994-01-18 Yale University Liposomal transfection of nucleic acids into animal cells
US5283185A (en) 1991-08-28 1994-02-01 University Of Tennessee Research Corporation Method for delivering nucleic acids into cells
EP0632722A4 (en) 1992-03-20 1997-07-30 Baylor College Medicine A dna transporter system and method of use.
ES2221920T3 (en) 1992-04-03 2005-01-16 The Regents Of The University Of California SELF-ASSEMBLY POLYUCLEOTID RELEASE SYSTEM THAT INCLUDES AN AMPHIPATIC CATIONIC PEPTIDE.
US5651981A (en) 1994-03-29 1997-07-29 Northwestern University Cationic phospholipids for transfection
US5527928A (en) 1994-09-30 1996-06-18 Nantz; Michael H. Cationic transport reagents

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060171935A1 (en) * 2005-01-31 2006-08-03 Asa Abeliovich Protecting cell therapy for neurological disorders including Parkinson's disease

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHRISTOPHER R SIBLEY ET AL: "Novel RNA-based Strategies for Therapeutic Gene Silencing", MOLECULAR THERAPY, vol. 18, no. 3, 1 March 2010 (2010-03-01), pages 466 - 476, XP055004655, ISSN: 1525-0016, DOI: 10.1038/mt.2009.306 *
SABATA MARTINO ET AL: "MicroRNA Implications across Neurodevelopment and Neuropathology", JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY, vol. 2009, 1 January 2009 (2009-01-01), pages 1 - 14, XP055004666, ISSN: 1110-7243, DOI: 10.1155/2009/654346 *
TAKAYUKI KUBODERA ET AL: "New RNAi Strategy for Selective Suppression of a Mutant Allele in Polyglutamine Disease", OLIGONUCLEOTIDES, vol. 15, no. 4, 1 December 2005 (2005-12-01), pages 298 - 302, XP055004760, ISSN: 1545-4576, DOI: 10.1089/oli.2005.15.298 *

Also Published As

Publication number Publication date
WO2011114106A2 (en) 2011-09-22
GB201004475D0 (en) 2010-05-05

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