CA2948844C - Engineering synthetic brain penetrating gene vectors - Google Patents

Engineering synthetic brain penetrating gene vectors Download PDF

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Publication number
CA2948844C
CA2948844C CA2948844A CA2948844A CA2948844C CA 2948844 C CA2948844 C CA 2948844C CA 2948844 A CA2948844 A CA 2948844A CA 2948844 A CA2948844 A CA 2948844A CA 2948844 C CA2948844 C CA 2948844C
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Prior art keywords
brain
formulation
nanoparticles
polymer
nanoparticle
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CA2948844A
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English (en)
French (fr)
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CA2948844A1 (en
Inventor
Justin Hanes
Jung Soo Suk
Panagiotis MASTORAKOS
Graeme WOODWORTH
Clark ZHANG
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Johns Hopkins University
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Johns Hopkins University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/0008—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0085—Brain, e.g. brain implants; Spinal cord
    • 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
    • A61K47/56—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • 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
    • A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6921—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
    • A61K47/6927—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
    • A61K47/6929—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
    • A61K47/6931—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer
    • A61K47/6935—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/0075—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the delivery route, e.g. oral, subcutaneous
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/513—Organic macromolecular compounds; Dendrimers
    • A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/513—Organic macromolecular compounds; Dendrimers
    • A61K9/5169—Proteins, e.g. albumin, gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5192—Processes
    • 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
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/88—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using amphiphile liposome vesicle

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Biomedical Technology (AREA)
  • Genetics & Genomics (AREA)
  • Nanotechnology (AREA)
  • Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Optics & Photonics (AREA)
  • Molecular Biology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Neurosurgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Psychology (AREA)
  • Neurology (AREA)
  • Immunology (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
CA2948844A 2014-05-12 2015-05-12 Engineering synthetic brain penetrating gene vectors Active CA2948844C (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201461991898P 2014-05-12 2014-05-12
US201461991920P 2014-05-12 2014-05-12
US61/991,898 2014-05-12
US61/991,920 2014-05-12
US201462001994P 2014-05-22 2014-05-22
US62/001,994 2014-05-22
PCT/US2015/030381 WO2015175539A1 (en) 2014-05-12 2015-05-12 Engineering synthetic brain penetrating gene vectors

Publications (2)

Publication Number Publication Date
CA2948844A1 CA2948844A1 (en) 2015-11-19
CA2948844C true CA2948844C (en) 2020-06-30

Family

ID=53264811

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2948844A Active CA2948844C (en) 2014-05-12 2015-05-12 Engineering synthetic brain penetrating gene vectors

Country Status (6)

Country Link
US (3) US9937270B2 (https=)
EP (1) EP3142704A1 (https=)
JP (2) JP6763780B2 (https=)
AU (1) AU2015259362B2 (https=)
CA (1) CA2948844C (https=)
WO (1) WO2015175539A1 (https=)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2538929A4 (en) 2010-02-25 2014-07-09 Univ Johns Hopkins DELAYED RELEASE OF THERAPIES IN A PART OF THE EYE
JP6824535B2 (ja) * 2015-09-11 2021-02-03 ザ・ジョンズ・ホプキンス・ユニバーシティー 脳間質内のナノ粒子分布を改善するための組成物および方法
US12496279B2 (en) 2019-04-11 2025-12-16 The Johns Hopkins University Nanoparticles for drug delivery to brain
CN111658785B (zh) * 2020-04-21 2023-05-12 威爱医疗科技(中山)有限公司 一种基因载体及其制备方法和应用

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5714331A (en) 1991-05-24 1998-02-03 Buchardt, Deceased; Ole Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5527675A (en) 1993-08-20 1996-06-18 Millipore Corporation Method for degradation and sequencing of polymers which sequentially eliminate terminal residues
DE4331012A1 (de) 1993-09-13 1995-03-16 Bayer Ag Nukleinsäuren-bindende Oligomere mit N-Verzweigung für Therapie und Diagnostik
US5786571A (en) 1997-05-09 1998-07-28 Lexmark International, Inc. Wrapped temperature sensing assembly
US6509323B1 (en) 1998-07-01 2003-01-21 California Institute Of Technology Linear cyclodextrin copolymers
EP1328253B1 (en) * 2000-04-26 2006-03-22 Oregon Health Sciences University Administration of a thiol-based chemoprotectant compound
WO2002003848A2 (en) 2000-07-10 2002-01-17 Naito Albert T Method for opening the blood-brain barrier
US20040259247A1 (en) 2000-12-01 2004-12-23 Thomas Tuschl Rna interference mediating small rna molecules
US7683036B2 (en) 2003-07-31 2010-03-23 Regulus Therapeutics Inc. Oligomeric compounds and compositions for use in modulation of small non-coding RNAs
US20050142581A1 (en) 2003-09-04 2005-06-30 Griffey Richard H. Microrna as ligands and target molecules
US20080213891A1 (en) 2004-07-21 2008-09-04 Alnylam Pharmaceuticals, Inc. RNAi Agents Comprising Universal Nucleobases
AU2005328382C1 (en) 2004-07-21 2013-01-24 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a modified or non-natural nucleobase
CA2574603C (en) 2004-08-04 2014-11-04 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase
US20060223777A1 (en) 2005-03-29 2006-10-05 Dharmacon, Inc. Highly functional short hairpin RNA
US20070213292A1 (en) 2005-08-10 2007-09-13 The Rockefeller University Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof
WO2007021896A2 (en) 2005-08-10 2007-02-22 Alnylam Pharmaceuticals, Inc. Chemically modified oligonucleotides for use in modulating micro rna and uses thereof
WO2007027894A2 (en) 2005-08-29 2007-03-08 Isis Pharmaceuticals, Inc. Antisense compounds having enhanced anti-microrna activity
CA2620856C (en) 2005-08-29 2017-11-28 Isis Pharmaceuticals, Inc. Methods for use in modulating mir-122a
US8658608B2 (en) 2005-11-23 2014-02-25 Yale University Modified triple-helix forming oligonucleotides for targeted mutagenesis
EP1984499B1 (en) 2006-01-27 2015-05-27 Isis Pharmaceuticals, Inc. Oligomeric compounds and compositions for the use in modulation of micrornas
CA2648132C (en) 2006-04-03 2019-05-28 Santaris Pharma A/S Pharmaceutical composition comprising anti-mirna antisense oligonucleotides
JP2008053276A (ja) 2006-08-22 2008-03-06 Nec Electronics Corp 半導体装置の製造方法
WO2008046911A2 (en) 2006-10-20 2008-04-24 Exiqon A/S Novel human micrornas associated with cancer
US20090137504A1 (en) 2006-12-21 2009-05-28 Soren Morgenthaler Echwald Microrna target site blocking oligos and uses thereof
WO2011133803A1 (en) 2010-04-21 2011-10-27 Helix Therapeutics, Inc. Compositions and methods for targeted inactivation of hiv cell surface receptors
US10307372B2 (en) 2010-09-10 2019-06-04 The Johns Hopkins University Rapid diffusion of large polymeric nanoparticles in the mammalian brain
CN103328038A (zh) * 2010-12-01 2013-09-25 史拜诺莫度雷森公司 向神经解剖结构直接递送药剂
WO2012109363A2 (en) * 2011-02-08 2012-08-16 The Johns Hopkins University Mucus penetrating gene carriers
CA2863964C (en) * 2012-02-07 2021-10-26 Global Bio Therapeutics Usa, Inc. Compartmentalized method of nucleic acid delivery and compositions and uses thereof

Also Published As

Publication number Publication date
WO2015175539A1 (en) 2015-11-19
JP2017515839A (ja) 2017-06-15
US20170087253A1 (en) 2017-03-30
US20200129641A1 (en) 2020-04-30
EP3142704A1 (en) 2017-03-22
JP6763780B2 (ja) 2020-09-30
US20180193488A1 (en) 2018-07-12
US9937270B2 (en) 2018-04-10
JP2020172534A (ja) 2020-10-22
AU2015259362A1 (en) 2016-12-01
AU2015259362B2 (en) 2018-02-15
CA2948844A1 (en) 2015-11-19
US10695442B2 (en) 2020-06-30

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