WO1999050425A3 - Regulated apoptosis using chemically induced dimerization of apoptosis factors - Google Patents

Regulated apoptosis using chemically induced dimerization of apoptosis factors Download PDF

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Publication number
WO1999050425A3
WO1999050425A3 PCT/US1999/006799 US9906799W WO9950425A3 WO 1999050425 A3 WO1999050425 A3 WO 1999050425A3 US 9906799 W US9906799 W US 9906799W WO 9950425 A3 WO9950425 A3 WO 9950425A3
Authority
WO
WIPO (PCT)
Prior art keywords
apoptosis
caspase
bcl
chemically
intracellular
Prior art date
Application number
PCT/US1999/006799
Other languages
French (fr)
Other versions
WO1999050425A2 (en
Inventor
David M Spencer
Kevin M Slawin
Original Assignee
Baylor College Medicine
David M Spencer
Kevin M Slawin
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 Baylor College Medicine, David M Spencer, Kevin M Slawin filed Critical Baylor College Medicine
Priority to AU34547/99A priority Critical patent/AU3454799A/en
Publication of WO1999050425A2 publication Critical patent/WO1999050425A2/en
Publication of WO1999050425A3 publication Critical patent/WO1999050425A3/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4873—Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2207/00—Modified animals
    • A01K2207/15—Humanized animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/20—Animal model comprising regulated expression system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/0331—Animal model for proliferative diseases
    • 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

Abstract

The present invention discloses artificial death switches (ADSs) based on chemically induced dimerization of the cysteine proteases, caspase-1 (ICE) and caspase-3 (YAMA). In both cases, aggregation of the target protein is achieved by a non-toxic, lipid-permeable, dimeric FK506 analog that binds to an attached FK506-binding protein (FKBP). The intracellular crosslinking of caspase-1 or caspase-3 is sufficient to trigger rapid apoptosis in a Bcl-xL-independent manner, suggesting that these conditional pro-apoptotic molecules can bypass intracellular checkpoint genes, like Bcl-xL, that limit apoptosis. Since these chimeric molecules are derived from autologous proteins, they should be non-immunogenic and thus ideal for long-lived gene therapy vectors. These properties should also make chemically-induced apoptosis (CIA) useful for developmental studies, for treating hyperproliferative disorders and for developing animal models to a wide variety of diseases.
PCT/US1999/006799 1998-03-30 1999-03-30 Regulated apoptosis using chemically induced dimerization of apoptosis factors WO1999050425A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU34547/99A AU3454799A (en) 1998-03-30 1999-03-30 Regulated apoptosis using chemically induced dimerization of apoptosis factors

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US7983198P 1998-03-30 1998-03-30
US60/079,831 1998-03-30

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US09647418 A-371-Of-International 2000-09-29
US10/247,019 Continuation US20040040047A1 (en) 1998-03-30 2002-09-19 Regulated apoptosis using chemically induced dimerization of apoptosis factors

Publications (2)

Publication Number Publication Date
WO1999050425A2 WO1999050425A2 (en) 1999-10-07
WO1999050425A3 true WO1999050425A3 (en) 1999-12-02

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/006799 WO1999050425A2 (en) 1998-03-30 1999-03-30 Regulated apoptosis using chemically induced dimerization of apoptosis factors

Country Status (2)

Country Link
AU (1) AU3454799A (en)
WO (1) WO1999050425A2 (en)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001021217A2 (en) * 1999-09-23 2001-03-29 Genvec, Inc. Method of treating cells of the prostate prophylactically or therapeutically
US6818444B2 (en) 2000-08-04 2004-11-16 Heska Corporation Canine and feline proteins, nucleic acid molecules and uses thereof
US7638331B2 (en) * 2004-01-02 2009-12-29 The Administration of the Tulane Rducation Fund Directed apoptosis in COX-2 overexpressing cancer cells through expression targeted gene delivery
GB201503133D0 (en) 2015-02-24 2015-04-08 Ucl Business Plc And Syncona Partners Llp Chimeric protein
GB201906126D0 (en) * 2019-05-01 2019-06-12 Autolus Ltd Chimeric protein
WO2021009299A1 (en) * 2019-07-17 2021-01-21 INSERM (Institut National de la Santé et de la Recherche Médicale) Bcl-xl:fkbp12 fusion proteins suitable for screening agents capable of slowing down the aging process

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995002684A1 (en) * 1993-07-16 1995-01-26 The Board Of Trustees Of The Leland Stanford Junior University Regulated apoptosis
WO1997020463A1 (en) * 1995-12-07 1997-06-12 The General Hospital Corporation Controlled gene product delivery from a regulatable retroviral vector
WO1997031898A1 (en) * 1996-02-28 1997-09-04 Ariad Gene Therapeutics, Inc. Synthetic derivatives of rapamycin as multimerizing agents for chimeric proteins with immunophilin-derived domains
WO1997031611A2 (en) * 1996-03-01 1997-09-04 Chiron Corporation Treatment of begnin prostatic hyperplasia

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995002684A1 (en) * 1993-07-16 1995-01-26 The Board Of Trustees Of The Leland Stanford Junior University Regulated apoptosis
WO1997020463A1 (en) * 1995-12-07 1997-06-12 The General Hospital Corporation Controlled gene product delivery from a regulatable retroviral vector
WO1997031898A1 (en) * 1996-02-28 1997-09-04 Ariad Gene Therapeutics, Inc. Synthetic derivatives of rapamycin as multimerizing agents for chimeric proteins with immunophilin-derived domains
WO1997031611A2 (en) * 1996-03-01 1997-09-04 Chiron Corporation Treatment of begnin prostatic hyperplasia

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
HENKART ET AL: "ICE FAMILY PROTEASES: MEDIATORS OF ALL APOPTOTIC CELL DEATH?", IMMUNITY, vol. 4, 1996, pages 195 - 201, XP002116598 *
MACCORKLE ET AL: "SYNTHETIC ACTIVATION OF CASPASES: ARTIFICIAL DEATH SWITCHES", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, USA, vol. 95, 31 March 1998 (1998-03-31), pages 3655 - 3660, XP002116599 *
MUZIO ET AL: "AN INDUCED PROXIMITY MODEL FOR CASPASE-8 ACTIVATION", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 273, 30 January 1998 (1998-01-30), pages 2926 - 2930, XP002116597 *
SLAWIN ET AL: "APOPTOSIS-INDUCTION IN BPH-DERIVED SMOOTH MUSCLE CELLS: PRECLINICAL STUDIES OF A NOVEL GENE THERAPEUTIC APPROACH TO BPH", JOURNAL OF UROLOGY, vol. 159, May 1998 (1998-05-01), pages 110, XP002116600 *

Also Published As

Publication number Publication date
AU3454799A (en) 1999-10-18
WO1999050425A2 (en) 1999-10-07

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