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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
Application number
PCT/US1996/012750
Other languages
English (en)
Other versions
WO1997004748A9 (fr
WO1997004748A2 (fr
WO1997004748B1 (fr
Inventor
Jon T Conary
Hans Schreier
Original Assignee
Advanced Therapies Inc
Jon T Conary
Hans Schreier
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, Jon T Conary, Hans Schreier 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

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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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Biophysics (AREA)
  • Dispersion Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biochemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Wood Science & Technology (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Plant Pathology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (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 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 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
US9562897B2 (en) 2010-09-30 2017-02-07 Raindance Technologies, Inc. Sandwich assays in droplets
US9562837B2 (en) 2006-05-11 2017-02-07 Raindance Technologies, Inc. Systems for handling microfludic droplets

Families Citing this family (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69708868T2 (de) 1996-04-12 2002-07-18 University Of Pittsburgh, Pittsburgh Neue kationische cholesterin derivate mit zyklischen polaren gruppen
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
CA2294579C (fr) * 1997-06-23 2007-10-09 Sequus Pharmaceuticals, Inc. Composition contenant un polynucleotidique piege dans des liposomes et procede correspondant
JP4298912B2 (ja) 1997-07-07 2009-07-22 メディカル リサーチ カウンシル ｉｎｖｉｔｒｏ選別法
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
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
AU2002231637A1 (en) * 2000-11-22 2002-06-03 Vectron Therapeutics Ag Production and use of a targeted diagnostic system
AU2002235141A1 (en) 2000-11-27 2002-06-03 Geron Corporation Glycosyltransferase vectors for treating cancer
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
AU2002251296A1 (en) * 2001-04-18 2002-10-28 The Open University Polypeptides derived from amyloid precursor peptide (app) and their uses
US7622446B2 (en) 2001-04-18 2009-11-24 The Open University Polypeptides, derivatives and uses thereof
WO2002088318A2 (fr) * 2001-04-30 2002-11-07 Targeted Genetics Corporation Complexes d'administration de medicaments contenant des lipides et leurs methodes de production
JP2005501011A (ja) * 2001-06-08 2005-01-13 ユタ ベンチャー ザ セカンド リミテッド パートナーシップ 組織特異的内皮膜タンパク質
EP1568379A1 (fr) 2002-11-01 2005-08-31 Genomidea Inc Preparation medicinale comprenant un agent chimiotherapeutique encapsule
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
IL296666A (en) 2005-03-23 2022-11-01 Genmab As Antibodies against cd38 for treatment of multiple myeloma
US8772046B2 (en) 2007-02-06 2014-07-08 Brandeis University Manipulation of fluids and reactions in microfluidic systems
WO2008130623A1 (fr) 2007-04-19 2008-10-30 Brandeis University Manipulation de fluides, composants fluidiques et réactions dans des systèmes microfluidiques
PL2222697T3 (pl) 2007-11-01 2013-05-31 Astellas Pharma Inc Immunosupresyjne polipeptydy i kwasy nukleinowe
US12038438B2 (en) 2008-07-18 2024-07-16 Bio-Rad Laboratories, Inc. Enzyme quantification
EP4047367A1 (fr) 2008-07-18 2022-08-24 Bio-Rad Laboratories, Inc. Procedé de détection d'analytes cibles au moyens des bibliothèques de gouttelettes
US8528589B2 (en) 2009-03-23 2013-09-10 Raindance Technologies, Inc. Manipulation of microfluidic droplets
WO2011042564A1 (fr) 2009-10-09 2011-04-14 Universite De Strasbourg Nanomatériau marqué à base de silice à propriétés améliorées et ses utilisations
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
EP3412778A1 (fr) 2011-02-11 2018-12-12 Raindance Technologies, Inc. Procédés permettant de former des gouttelettes mélangées
EP2675819B1 (fr) 2011-02-18 2020-04-08 Bio-Rad Laboratories, Inc. Compositions et méthodes de marquage moléculaire
EP3709018A1 (fr) 2011-06-02 2020-09-16 Bio-Rad Laboratories, Inc. Appareil microfluidique pour l'identification de composants d'une reaction chimique
US8658430B2 (en) 2011-07-20 2014-02-25 Raindance Technologies, Inc. Manipulating droplet size
WO2013142514A1 (fr) * 2012-03-19 2013-09-26 Isis Pharmaceuticals, Inc. Procédés et compositions destinés à la modulation de l'expression de l'alpha-1-antitrypsine
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
IL278665B2 (en) * 2018-05-15 2024-10-01 Flagship Pioneering Innovations V Inc Fusosome compositions and uses thereof
AU2019301053A1 (en) 2018-07-09 2021-01-28 Flagship Pioneering Innovations V, Inc. Fusosome compositions and uses thereof

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
AU6691496A (en) 1997-02-26
WO1997004748A2 (fr) 1997-02-13

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