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WO1997004748A3 - Enveloppes virales artificielles renforcees pour l'apport de substances therapeutiques dans les cellules - Google Patents

Enveloppes virales artificielles renforcees pour l'apport de substances therapeutiques dans les cellules Download PDF

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Publication number
WO1997004748A3
WO1997004748A3 PCT/US1996/012750 US9612750W WO9704748A3 WO 1997004748 A3 WO1997004748 A3 WO 1997004748A3 US 9612750 W US9612750 W US 9612750W WO 9704748 A3 WO9704748 A3 WO 9704748A3
Authority
WO
WIPO (PCT)
Prior art keywords
vesicles
therapeutic substances
artificial viral
envelopes
nucleic acid
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US1996/012750
Other languages
English (en)
Other versions
WO1997004748B1 (fr
WO1997004748A2 (fr
WO1997004748A9 (fr
Inventor
Jon T Conary
Hans Schreier
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Advanced Therapies Inc
Original Assignee
Advanced Therapies Inc
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 Advanced Therapies Inc filed Critical Advanced Therapies Inc
Priority to AU66914/96A priority Critical patent/AU6691496A/en
Publication of WO1997004748A2 publication Critical patent/WO1997004748A2/fr
Publication of WO1997004748A3 publication Critical patent/WO1997004748A3/fr
Publication of WO1997004748B1 publication Critical patent/WO1997004748B1/fr
Publication of WO1997004748A9 publication Critical patent/WO1997004748A9/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
    • C07K14/8121—Serpins
    • C07K14/8125—Alpha-1-antitrypsin
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Dispersion Chemistry (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des enveloppes virales artificielles et d'autres vésicules lipidiques qui encapsulent des substances thérapeutiques telles que des vecteurs d'expression visant des cellules de mammifères. Les polynucléotides peuvent être mis dans les enveloppes par compression à l'avance avec un peptide court ayant une charge positive prédominante. L'opération de compression non seulement facilite l'encapsulation mais elle augmente aussi le nombre de vésicules contenant de l'acide nucléique, réduit au minimum la quantité d'acide nucléique libre, et elle peut aussi augmenter la taille et la complexité des plasmides qui peuvent être encapsulés. Les vésicules peuvent être pourvues d'un constituant ciblant des tissus, qui aide à les diriger vers certains sites tissulaires d'un animal, et elles peuvent aussi être pourvues d'un constituant fusogénique qui facilite l'apport de la substance thérapeutique dans la cellule. Les substances et les réactifs selon la présente invention sont efficaces, par exemple, pour accroître l'expression de protéines modèles à la fois dans des cellules isolées et chez des animaux intacts, et on s'attend à ce qu'ils soient utiles pour la thérapie génique.
PCT/US1996/012750 1995-08-01 1996-08-01 Enveloppes virales artificielles renforcees pour l'apport de substances therapeutiques dans les cellules Ceased WO1997004748A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU66914/96A AU6691496A (en) 1995-08-01 1996-08-01 Enhanced artificial viral envelopes for cellular delivery of therapeutic substances

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US173895P 1995-08-01 1995-08-01
US60/001,738 1995-08-01
US258095P 1995-08-21 1995-08-21
US60/002,580 1995-08-21
US69061396A 1996-07-31 1996-07-31
US60/690,613 1996-07-31

Publications (4)

Publication Number Publication Date
WO1997004748A2 WO1997004748A2 (fr) 1997-02-13
WO1997004748A3 true WO1997004748A3 (fr) 1997-05-29
WO1997004748B1 WO1997004748B1 (fr) 1997-07-17
WO1997004748A9 WO1997004748A9 (fr) 1997-10-09

Family

ID=27356985

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/012750 Ceased WO1997004748A2 (fr) 1995-08-01 1996-08-01 Enveloppes virales artificielles renforcees pour l'apport de substances therapeutiques dans les cellules

Country Status (2)

Country Link
AU (1) AU6691496A (fr)
WO (1) WO1997004748A2 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7335509B2 (en) 1995-01-23 2008-02-26 University Of Pittsburgh Stable lipid-comprising drug delivery complexes and methods for their production
US8841071B2 (en) 2011-06-02 2014-09-23 Raindance Technologies, Inc. Sample multiplexing
US8871444B2 (en) 2004-10-08 2014-10-28 Medical Research Council In vitro evolution in microfluidic systems
US9012390B2 (en) 2006-08-07 2015-04-21 Raindance Technologies, Inc. Fluorocarbon emulsion stabilizing surfactants
US9228229B2 (en) 2010-02-12 2016-01-05 Raindance Technologies, Inc. Digital analyte analysis
US9273308B2 (en) 2006-05-11 2016-03-01 Raindance Technologies, Inc. Selection of compartmentalized screening method
US9328344B2 (en) 2006-01-11 2016-05-03 Raindance Technologies, Inc. Microfluidic devices and methods of use in the formation and control of nanoreactors
US9366632B2 (en) 2010-02-12 2016-06-14 Raindance Technologies, Inc. Digital analyte analysis
US9399797B2 (en) 2010-02-12 2016-07-26 Raindance Technologies, Inc. Digital analyte analysis
US9448172B2 (en) 2003-03-31 2016-09-20 Medical Research Council Selection by compartmentalised screening
US9498759B2 (en) 2004-10-12 2016-11-22 President And Fellows Of Harvard College Compartmentalized screening by microfluidic control
US9562837B2 (en) 2006-05-11 2017-02-07 Raindance Technologies, Inc. Systems for handling microfludic droplets
US9562897B2 (en) 2010-09-30 2017-02-07 Raindance Technologies, Inc. Sandwich assays in droplets

Families Citing this family (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2251543A1 (fr) 1996-04-12 1997-10-23 University Of Pittsburgh Nouveaux derives de cholesteryle cationiques contenant des groupes polaires cycliques
US6258792B1 (en) 1996-04-12 2001-07-10 University Of Pittsburgh Cationic cholesteryl derivatives containing cyclic polar groups
FR2751222B1 (fr) * 1996-07-16 1998-10-09 Capsulis Compositions contenant au moins un acide nucleique et leurs applications dans le domaine biomedical, en particulier en therapie genique
ATE255882T1 (de) * 1997-06-23 2003-12-15 Sequus Pharm Inc Liposomen-umschlossene polynukleotidzusammensetzung sowie verfahren
CA2295324C (fr) 1997-07-07 2012-12-18 Andrew Griffiths Procede de selection in vitro
FR2766705B1 (fr) * 1997-07-30 2001-05-25 Biovector Therapeutics Complexe particulaire de charge globale neutre ou negative forme d'une vesicule cationique ou neutre et d'une substance biologiquement active anionique, leur preparation et leur utilisation
FR2766706B1 (fr) * 1997-07-30 2001-05-25 Biovector Therapeutics Sa Complexes particulaires stables de charge globale neutre ou negative de structure multilamellaire composes par au moins une substance biologiquement active globalement anionique et un constituant cationique, leur preparation et utilisation
US6372720B1 (en) * 1998-02-05 2002-04-16 Kenneth J. Longmuir Liposome fusion and delivery vehicle
US20030021792A1 (en) * 2001-06-08 2003-01-30 Roben Paul W. Tissue-specific endothelial membrane proteins
US6903196B1 (en) 1999-06-17 2005-06-07 Utah Ventures Ii, L.P. Methods for identifying and isolating tissue-specific lumen-exposed molecules
GB0015624D0 (en) * 2000-06-26 2000-08-16 Nat Cancer Centre Materials and methods relating to improved gene delivery
WO2002041870A2 (fr) * 2000-11-22 2002-05-30 Vectron Therapeutics Ag Production et utilisation d'un systeme de diagnostic cible
AU2002235141A1 (en) 2000-11-27 2002-06-03 Geron Corporation Glycosyltransferase vectors for treating cancer
US7622446B2 (en) 2001-04-18 2009-11-24 The Open University Polypeptides, derivatives and uses thereof
IL158435A0 (en) * 2001-04-18 2004-05-12 Univ Open Polypeptides, derivatives and uses thereof
US7491702B2 (en) 2001-04-18 2009-02-17 The Open University Polypeptides related to amyloid precursor protein, pharmaceutical compositions thereof, and methods of treatment using the same
US20030203865A1 (en) * 2001-04-30 2003-10-30 Pierrot Harvie Lipid-comprising drug delivery complexes and methods for their production
JP4746877B2 (ja) * 2002-11-01 2011-08-10 ジェノミディア株式会社 不活性化されたセンダイウイルスエンベロープを有効成分とする抗癌剤
GB0307428D0 (en) 2003-03-31 2003-05-07 Medical Res Council Compartmentalised combinatorial chemistry
US20060078893A1 (en) 2004-10-12 2006-04-13 Medical Research Council Compartmentalised combinatorial chemistry by microfluidic control
EA015584B1 (ru) 2005-03-23 2011-10-31 Генмаб А/С Антитело к cd38 человека и его применение
US8772046B2 (en) 2007-02-06 2014-07-08 Brandeis University Manipulation of fluids and reactions in microfluidic systems
US8592221B2 (en) 2007-04-19 2013-11-26 Brandeis University Manipulation of fluids, fluid components and reactions in microfluidic systems
PT2612868T (pt) 2007-11-01 2018-10-24 Astellas Pharma Inc Ácidos nucleicos e polipéptidos imunosupressores
WO2010009365A1 (fr) 2008-07-18 2010-01-21 Raindance Technologies, Inc. Bibliothèque de gouttelettes
US12038438B2 (en) 2008-07-18 2024-07-16 Bio-Rad Laboratories, Inc. Enzyme quantification
EP2411148B1 (fr) 2009-03-23 2018-02-21 Raindance Technologies, Inc. Manipulation de gouttelettes microfluidiques
US10520500B2 (en) 2009-10-09 2019-12-31 Abdeslam El Harrak Labelled silica-based nanomaterial with enhanced properties and uses thereof
US10837883B2 (en) 2009-12-23 2020-11-17 Bio-Rad Laboratories, Inc. Microfluidic systems and methods for reducing the exchange of molecules between droplets
US10351905B2 (en) 2010-02-12 2019-07-16 Bio-Rad Laboratories, Inc. Digital analyte analysis
US9364803B2 (en) 2011-02-11 2016-06-14 Raindance Technologies, Inc. Methods for forming mixed droplets
US9150852B2 (en) 2011-02-18 2015-10-06 Raindance Technologies, Inc. Compositions and methods for molecular labeling
US9556470B2 (en) 2011-06-02 2017-01-31 Raindance Technologies, Inc. Enzyme quantification
US8658430B2 (en) 2011-07-20 2014-02-25 Raindance Technologies, Inc. Manipulating droplet size
US9340784B2 (en) * 2012-03-19 2016-05-17 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating alpha-1-antitrypsin expression
US11901041B2 (en) 2013-10-04 2024-02-13 Bio-Rad Laboratories, Inc. Digital analysis of nucleic acid modification
US9944977B2 (en) 2013-12-12 2018-04-17 Raindance Technologies, Inc. Distinguishing rare variations in a nucleic acid sequence from a sample
EP3090063B1 (fr) 2013-12-31 2019-11-06 Bio-Rad Laboratories, Inc. Procédé de détection de rétrovirus latent
US10647981B1 (en) 2015-09-08 2020-05-12 Bio-Rad Laboratories, Inc. Nucleic acid library generation methods and compositions
EP3793570A2 (fr) * 2018-05-15 2021-03-24 Flagship Pioneering Innovations V, Inc. Compositions de fusosome et leurs utilisations
MX2021000308A (es) 2018-07-09 2021-06-08 Flagship Pioneering Innovations V Inc Composiciones de fusosoma y usos de estas.

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0475178A1 (fr) * 1990-08-27 1992-03-18 Kabushiki Kaisha Vitamin Kenkyusyo Liposome pour envelopper un gène, préparation liposomale et procédé de manufacture de la préparation
EP0497997A1 (fr) * 1991-02-02 1992-08-12 Nika Health Products Limited Vésicules membranaires synthétiques contenant des peptides de fusion fonctionellement actifs comme systèmes de délivrance d'un médicament
EP0544292A2 (fr) * 1991-11-27 1993-06-02 Roche Diagnostics GmbH Méthode d'introduction d'acides nucléiques dans des cellules
WO1994018947A1 (fr) * 1993-02-16 1994-09-01 Sharifa Karali Complexe protamine-adn de haute purete et son utilisation
WO1996040964A2 (fr) * 1995-06-07 1996-12-19 Inex Pharmaceuticals Corporation Particules d'acides nucleiques et de lipides preparees au moyen d'un intermediaire de complexe hydrophobe d'acides nucleiques et de lipides et utilisation pour transferer des genes

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0475178A1 (fr) * 1990-08-27 1992-03-18 Kabushiki Kaisha Vitamin Kenkyusyo Liposome pour envelopper un gène, préparation liposomale et procédé de manufacture de la préparation
EP0497997A1 (fr) * 1991-02-02 1992-08-12 Nika Health Products Limited Vésicules membranaires synthétiques contenant des peptides de fusion fonctionellement actifs comme systèmes de délivrance d'un médicament
EP0544292A2 (fr) * 1991-11-27 1993-06-02 Roche Diagnostics GmbH Méthode d'introduction d'acides nucléiques dans des cellules
WO1994018947A1 (fr) * 1993-02-16 1994-09-01 Sharifa Karali Complexe protamine-adn de haute purete et son utilisation
WO1996040964A2 (fr) * 1995-06-07 1996-12-19 Inex Pharmaceuticals Corporation Particules d'acides nucleiques et de lipides preparees au moyen d'un intermediaire de complexe hydrophobe d'acides nucleiques et de lipides et utilisation pour transferer des genes

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7335509B2 (en) 1995-01-23 2008-02-26 University Of Pittsburgh Stable lipid-comprising drug delivery complexes and methods for their production
US7361640B2 (en) 1995-01-23 2008-04-22 University Of Pittsburgh Stable lipid-comprising drug delivery complexes and methods for their production
US9448172B2 (en) 2003-03-31 2016-09-20 Medical Research Council Selection by compartmentalised screening
US8871444B2 (en) 2004-10-08 2014-10-28 Medical Research Council In vitro evolution in microfluidic systems
US9186643B2 (en) 2004-10-08 2015-11-17 Medical Research Council In vitro evolution in microfluidic systems
US9498759B2 (en) 2004-10-12 2016-11-22 President And Fellows Of Harvard College Compartmentalized screening by microfluidic control
US9328344B2 (en) 2006-01-11 2016-05-03 Raindance Technologies, Inc. Microfluidic devices and methods of use in the formation and control of nanoreactors
US9410151B2 (en) 2006-01-11 2016-08-09 Raindance Technologies, Inc. Microfluidic devices and methods of use in the formation and control of nanoreactors
US9534216B2 (en) 2006-01-11 2017-01-03 Raindance Technologies, Inc. Microfluidic devices and methods of use in the formation and control of nanoreactors
US9273308B2 (en) 2006-05-11 2016-03-01 Raindance Technologies, Inc. Selection of compartmentalized screening method
US9562837B2 (en) 2006-05-11 2017-02-07 Raindance Technologies, Inc. Systems for handling microfludic droplets
US9012390B2 (en) 2006-08-07 2015-04-21 Raindance Technologies, Inc. Fluorocarbon emulsion stabilizing surfactants
US9498761B2 (en) 2006-08-07 2016-11-22 Raindance Technologies, Inc. Fluorocarbon emulsion stabilizing surfactants
US9228229B2 (en) 2010-02-12 2016-01-05 Raindance Technologies, Inc. Digital analyte analysis
US9366632B2 (en) 2010-02-12 2016-06-14 Raindance Technologies, Inc. Digital analyte analysis
US9399797B2 (en) 2010-02-12 2016-07-26 Raindance Technologies, Inc. Digital analyte analysis
US9562897B2 (en) 2010-09-30 2017-02-07 Raindance Technologies, Inc. Sandwich assays in droplets
US8841071B2 (en) 2011-06-02 2014-09-23 Raindance Technologies, Inc. Sample multiplexing

Also Published As

Publication number Publication date
WO1997004748A2 (fr) 1997-02-13
AU6691496A (en) 1997-02-26

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