WO2009083738A3 - Rna delivery vehicles - Google Patents

Rna delivery vehicles Download PDF

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Publication number
WO2009083738A3
WO2009083738A3 PCT/GB2008/051232 GB2008051232W WO2009083738A3 WO 2009083738 A3 WO2009083738 A3 WO 2009083738A3 GB 2008051232 W GB2008051232 W GB 2008051232W WO 2009083738 A3 WO2009083738 A3 WO 2009083738A3
Authority
WO
WIPO (PCT)
Prior art keywords
dsna
target cell
delivery vehicles
guide strand
delivery vehicle
Prior art date
Application number
PCT/GB2008/051232
Other languages
French (fr)
Other versions
WO2009083738A2 (en
Inventor
John Chaddock
Matthew Beard
Original Assignee
Syntaxin 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 Syntaxin Limited filed Critical Syntaxin Limited
Publication of WO2009083738A2 publication Critical patent/WO2009083738A2/en
Publication of WO2009083738A3 publication Critical patent/WO2009083738A3/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
    • A61K47/6455—Polycationic oligopeptides, polypeptides or polyamino acids, e.g. for complexing nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6415—Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6435—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the peptide or protein in the drug conjugate being a connective tissue peptide, e.g. collagen, fibronectin or gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents

Abstract

The present invention relates to double stranded nucleic acid (dsNA) delivery vehicles comprising a dsNA, and a clostridial endosomal translocation domain. Said delivery vehicle may further comprise a non-cytotoxic protease and/ or a Targeting Moiety (TM). The present invention also provides a method for delivering an RNA guide strand into a target cell, and to the use of a dsNA delivery vehicle for down-regulating mRNAactivity in a target cell. In one embodiment, the RNA guide strand binds to a SNARE mRNA target sequence, which leads to the suppression of SNARE protein expression in the target cell.
PCT/GB2008/051232 2007-12-31 2008-12-31 Rna delivery vehicles WO2009083738A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0725321.4 2007-12-31
GBGB0725321.4A GB0725321D0 (en) 2007-12-31 2007-12-31 Delivery vehicles

Publications (2)

Publication Number Publication Date
WO2009083738A2 WO2009083738A2 (en) 2009-07-09
WO2009083738A3 true WO2009083738A3 (en) 2009-08-27

Family

ID=39092456

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2008/051232 WO2009083738A2 (en) 2007-12-31 2008-12-31 Rna delivery vehicles

Country Status (2)

Country Link
GB (1) GB0725321D0 (en)
WO (1) WO2009083738A2 (en)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4082551A1 (en) 2006-08-08 2022-11-02 Rheinische Friedrich-Wilhelms-Universität Bonn Structure and use of 5' phosphate oligonucleotides
EP2297323A1 (en) 2008-05-21 2011-03-23 Hartmann, Gunther 5' triphosphate oligonucleotide with blunt end and uses thereof
GB0815264D0 (en) 2008-08-21 2008-09-24 Syntaxin Ltd Non-cytotoxic proteins
WO2011133658A1 (en) * 2010-04-22 2011-10-27 Boston Medical Center Corporation Compositions and methods for targeting and delivering therapeutics into cells
EP2508530A1 (en) 2011-03-28 2012-10-10 Rheinische Friedrich-Wilhelms-Universität Bonn Purification of triphosphorylated oligonucleotides using capture tags
GB201108108D0 (en) * 2011-05-16 2011-06-29 Syntaxin Ltd Therapeutic fusion proteins
EP2712870A1 (en) 2012-09-27 2014-04-02 Rheinische Friedrich-Wilhelms-Universität Bonn Novel RIG-I ligands and methods for producing them
US10975388B2 (en) 2016-12-14 2021-04-13 Ligandal, Inc. Methods and compositions for nucleic acid and protein payload delivery
US11197928B2 (en) 2017-01-13 2021-12-14 Board Of Regents, The University Of Texas System Sustained production of high affinity antigen specific antibody by high dose BAFF receptor-targeting mAb-siRNA conjugate
GB201914034D0 (en) * 2019-09-30 2019-11-13 Ipsen Biopharm Ltd Treatment of neurological disorders
EP4311579A1 (en) 2022-07-29 2024-01-31 Association Française contre les Myopathies B cell-specific mab-sirna conjugates improve myasthenia

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997020579A2 (en) * 1995-12-05 1997-06-12 Smithkline Beecham Plc Novel compounds and use
WO2000033880A2 (en) * 1998-12-04 2000-06-15 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Conjugate used for enriching in neuronal cells
US20060024331A1 (en) * 2004-08-02 2006-02-02 Ester Fernandez-Salas Toxin compounds with enhanced membrane translocation characteristics
WO2006059105A2 (en) * 2004-12-01 2006-06-08 Health Protection Agency Non-cytotoxic Protein Conjugates
WO2008094583A2 (en) * 2007-01-30 2008-08-07 The General Hospital Corporation Methods and devices for mri-based measurement of axonal transport in vivo and delivery of therapeutic substances to the cns

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997020579A2 (en) * 1995-12-05 1997-06-12 Smithkline Beecham Plc Novel compounds and use
WO2000033880A2 (en) * 1998-12-04 2000-06-15 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Conjugate used for enriching in neuronal cells
US20060024331A1 (en) * 2004-08-02 2006-02-02 Ester Fernandez-Salas Toxin compounds with enhanced membrane translocation characteristics
WO2006059105A2 (en) * 2004-12-01 2006-06-08 Health Protection Agency Non-cytotoxic Protein Conjugates
WO2008094583A2 (en) * 2007-01-30 2008-08-07 The General Hospital Corporation Methods and devices for mri-based measurement of axonal transport in vivo and delivery of therapeutic substances to the cns

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
BADE S ET AL: "Botulinum neurotoxin type D enables cytosolic delivery of enzymatically active cargo proteins to neurons via unfolded translocation intermediates", JOURNAL OF NEUROCHEMISTRY, NEW YORK, NY, US, vol. 91, 1 January 2004 (2004-01-01), pages 1461 - 1472, XP002385397, ISSN: 0022-3042 *
CHADDOCK J A ET AL: "Clostridial neurotoxins: structure-function led design of new therapeutics", CMLS CELLULAR AND MOLECULAR LIFE SCIENCES, BIRKHÄUSER-VERLAG, BA, vol. 63, no. 5, 1 March 2006 (2006-03-01), pages 540 - 551, XP019201042, ISSN: 1420-9071 *
CHIU Y-L ET AL: "VISUALIZING A CORRELATON BETWEEN SIRNA LOCALIZATION, CELLULAR UPTAKE, AND RNAI IN LIVING CELLS", CHEMISTRY AND BIOLOGY, CURRENT BIOLOGY, LONDON, GB, vol. 11, no. 8, 1 August 2004 (2004-08-01), pages 1165 - 1175, XP008066695, ISSN: 1074-5521 *
DE FOUGEROLLES ANTONIN R: "Delivery vehicles for small interfering RNA in vivo", HUMAN GENE THERAPY, vol. 19, no. 2, February 2008 (2008-02-01), pages 125 - 132, XP002522155, ISSN: 1043-0342 *
FOSTER K A ET AL: "Re-engineering the target specificity of Clostridial neurotoxins - a route to novel therapeutics", NEUROTOXICITY RESEARCH, HARWOOD ACADEMIC PUBLISHERS, LAUSANNE, vol. 9, no. 2-3, 1 April 2006 (2006-04-01), pages 101 - 107, XP009089826, ISSN: 1029-8428 *
KNIGHT A ET AL: "NON-VIRAL NEURONAL GENE DELIVERY MEDIATED BY THE HC FRAGMENT OF TETANUS TOXIN", EUROPEAN JOURNAL OF BIOCHEMISTRY, BLACKWELL PUBLISHING, BERLIN, DE, vol. 259, no. 3, 1 February 1999 (1999-02-01), pages 762 - 769, XP000874380, ISSN: 0014-2956 *
KUMAR PRITI ET AL: "Transvascular delivery of small interfering RNA to the central nervous system", NATURE, NATURE PUBLISHING GROUP, LONDON, UK, vol. 448, no. 7149, 5 July 2007 (2007-07-05), pages 39 - 45, XP002499820, ISSN: 0028-0836 *
STEVENS JAMES ET AL: "Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus", SCIENCE (WASHINGTON D C), vol. 312, no. 5772, April 2006 (2006-04-01), pages 404 - 410, XP002533276, ISSN: 0036-8075 *

Also Published As

Publication number Publication date
GB0725321D0 (en) 2008-02-06
WO2009083738A2 (en) 2009-07-09

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