WO2000078986B1 - Regulation system of expression using nuclear ppar receptors - Google Patents

Regulation system of expression using nuclear ppar receptors

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Publication number
WO2000078986B1
WO2000078986B1 PCT/FR2000/001744 FR0001744W WO0078986B1 WO 2000078986 B1 WO2000078986 B1 WO 2000078986B1 FR 0001744 W FR0001744 W FR 0001744W WO 0078986 B1 WO0078986 B1 WO 0078986B1
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WO
WIPO (PCT)
Prior art keywords
composition according
ppar
nucleic acid
promoter
vector
Prior art date
Application number
PCT/FR2000/001744
Other languages
French (fr)
Other versions
WO2000078986A1 (en
Inventor
Raphael Darteil
Joel Crouzet
Bart Staels
Abderrahim Mahfoudi
Original Assignee
Aventis Pharma Sa
Raphael Darteil
Joel Crouzet
Bart Staels
Abderrahim Mahfoudi
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
Priority claimed from FR9907957A external-priority patent/FR2795425B1/en
Priority to BR0011897-4A priority Critical patent/BR0011897A/en
Priority to IL14710400A priority patent/IL147104A0/en
Priority to KR1020017016447A priority patent/KR20020028909A/en
Priority to MXPA01013227A priority patent/MXPA01013227A/en
Priority to HU0203584A priority patent/HUP0203584A2/en
Priority to PL00353031A priority patent/PL353031A1/en
Priority to CA002375869A priority patent/CA2375869A1/en
Application filed by Aventis Pharma Sa, Raphael Darteil, Joel Crouzet, Bart Staels, Abderrahim Mahfoudi filed Critical Aventis Pharma Sa
Priority to AU61645/00A priority patent/AU6164500A/en
Priority to NZ516678A priority patent/NZ516678A/en
Priority to EP00948058A priority patent/EP1190084A1/en
Priority to JP2001505726A priority patent/JP2003503034A/en
Publication of WO2000078986A1 publication Critical patent/WO2000078986A1/en
Publication of WO2000078986B1 publication Critical patent/WO2000078986B1/en
Priority to NO20016347A priority patent/NO20016347L/en

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    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/001—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination
    • C12N2830/002—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination inducible enhancer/promoter combination, e.g. hypoxia, iron, transcription factor
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/42—Vector systems having a special element relevant for transcription being an intron or intervening sequence for splicing and/or stability of RNA
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/80—Vector systems having a special element relevant for transcription from vertebrates
    • C12N2830/85—Vector systems having a special element relevant for transcription from vertebrates mammalian
    • 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
    • C12N2840/00—Vectors comprising a special translation-regulating system
    • C12N2840/20—Vectors comprising a special translation-regulating system translation of more than one cistron

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Toxicology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Cell Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention concerns novel methods and compositions for the pharmacological regulation of the expression of transgenes. More particularly, it concerns a composition comprising: (a) a first element comprising a nucleic acid of interest under the control of an inducible promoter comprising an element containing a response element to a PPAR and a minimal transcriptional receptor; and (b) a second element comprising a nucleic acid coding for a PPAR under the control of a transcriptional promoter, for simultaneous, separate or prolonged use. The invention concerns the use of said compositions and methods in the experimental, clinical, therapeutic or diagnostic fields.

Claims

48REVENDICATIONS MODIFIEES[reçues par le Bureau international le 3 janvier 2001 (03.01.01); revendications originales 1-30 remplacées par les nouvelles revendications 1-33 (4 pages)] 48 MODIFIED CLAIMS [received by the International Bureau on January 3, 2001 (03.01.01); original claims 1-30 replaced by new claims 1-33 (4 pages)]
1. Composition comprenant :1. Composition including:
(a) un premier élément comprenant un acide nucléique d'intérêt sous contrôle d'un promoteur inductible comprenant un élément de réponse à un PPAR et un promoteur transcriptionnel minimal, et(a) a first element comprising a nucleic acid of interest under the control of an inducible promoter comprising a response element to a PPAR and a minimal transcriptional promoter, and
(b) un deuxième élément comprenant un acide nucléique codant un PPAR sous contrôle d'un promoteur transcriptionnel, en vue de leur utilisation simultanée, séparée ou espacée dans le temps.(b) a second element comprising a nucleic acid encoding a PPAR under the control of a transcriptional promoter, with a view to their simultaneous, separate or spaced-apart use over time.
2. Composition selon la revendication 1 , caractérisée en ce qu'elle comprend en outre:2. Composition according to claim 1, characterized in that it further comprises:
(c) un ligand de PPAR. en vue d'une utilisation simultanée, séparée ou espacée dans le temps.(c) a PPAR ligand. for simultaneous, separate or time-separated use.
3. Composition selon la revendication 1 ou 2, caractérisée en ce que les éléments (a) et (b) sont portés par des constructions génétiques distinctes.3. Composition according to claim 1 or 2, characterized in that the elements (a) and (b) are carried by separate genetic constructions.
4. Composition selon la revendication 1 ou 2, caractérisée en ce que les éléments (a) et (b) sont assemblés dans une même construction génétique.4. Composition according to claim 1 or 2, characterized in that the elements (a) and (b) are assembled in the same genetic construction.
5. Composition selon la revendication 3 ou 4, caractérisée en ce que la construction génétique est un vecteur plasmidique ou viral.5. Composition according to claim 3 or 4, characterized in that the genetic construction is a plasmid or viral vector.
6. Composition selon la revendication 5, caractérisée en ce que le vecteur viral est un virus adéno-associé (AAV).6. Composition according to claim 5, characterized in that the viral vector is an adeno-associated virus (AAV).
7. Composition selon l'une des revendications 1 à 6, caractérisée en ce que l'élément de réponse à un PPAR comprend un ou plusieurs sites de liaison du PPAR.7. Composition according to one of claims 1 to 6, characterized in that the response element to a PPAR comprises one or more binding sites of the PPAR.
8. Composition selon la revendication 7, caractérisée en ce que l'élément de réponse à un PPAR comprend un ou plusieurs sites de séquence SEQ ID NO:1 ou de variants fonctionnels de cette séquence. 8. Composition according to claim 7, characterized in that the response element to a PPAR comprises one or more sites of sequence SEQ ID NO: 1 or of functional variants of this sequence.
9. Composition selon la revendication 7, caractérisée en ce que l'élément de réponse à un PPAR comprend un ou plusieurs sites de séquence SEQ ID NO: 5 ou de variants fonctionnels de cette séquence.9. Composition according to claim 7, characterized in that the response element to a PPAR comprises one or more sites of sequence SEQ ID NO: 5 or of functional variants of this sequence.
10. Composition selon les revendications 7 à 9, caractérisée en ce que l'élément de réponse comprend jusqu'à 30 sites de liaison, de préférence de 3 à 20, plus préférentiellement de 5 à 15.10. Composition according to claims 7 to 9, characterized in that the response element comprises up to 30 binding sites, preferably from 3 to 20, more preferably from 5 to 15.
11. Composition selon l'une des revendications 1 à 10, caractérisée en ce que le promoteur minimal est un promoteur d'un gène cellulaire ou viral délété de région(s) non essentielle(s) à l'activité transcriptionnelle.11. Composition according to one of claims 1 to 10, characterized in that the minimal promoter is a promoter of a cellular or viral gene deleted from region (s) not essential (s) to transcriptional activity.
12. Composition selon l'une des revendications 1 à 11 , caractérisée en ce que le promoteur inductible comprend en outre une région amplificatrice.12. Composition according to one of claims 1 to 11, characterized in that the inducible promoter further comprises an amplifying region.
13. Composition selon l'une des revendications 1 à 12, caractérisée en ce que le promoteur minimal et l'élément de réponse à un PPAR sont dans la même orientation.13. Composition according to one of claims 1 to 12, characterized in that the minimum promoter and the response element to a PPAR are in the same orientation.
14. Composition selon l'une des revendications 1 à 12, caractérisée en ce que le promoteur minimal et l'élément de réponse à un PPAR sont en orientation inverse.14. Composition according to one of claims 1 to 12, characterized in that the minimum promoter and the response element to a PPAR are in reverse orientation.
15. Composition selon l'une des revendications 1 à 14, caractérisée en ce que l'acide nucléique codant un PPAR code un PPARα ou un PPARγ.15. Composition according to one of claims 1 to 14, characterized in that the nucleic acid coding for a PPAR codes for a PPARα or a PPARγ.
16. Composition selon l'une des revendications 1 à 15, caractérisée en ce que l'acide nucléique codant un PPAR code un PPAR modifié comprenant plusieurs sites de liaison au ligand.16. Composition according to one of claims 1 to 15, characterized in that the nucleic acid coding for a PPAR codes for a modified PPAR comprising several ligand binding sites.
17. Composition selon l'une des revendications 1 à 16, caractérisée en ce qu'elle comprend en outre un élément (d) comprenant un acide nucléique codant un RXR sous le contrôle d'un promoteur transcriptionnel. 17. Composition according to one of claims 1 to 16, characterized in that it further comprises an element (d) comprising a nucleic acid encoding an RXR under the control of a transcriptional promoter.
18. Vecteur comprenant un élément (a) et un élément (b) selon la revendication 1.18. Vector comprising an element (a) and an element (b) according to claim 1.
19. Vecteur selon la revendication 18, caractérisé en ce que les éléments (a) et (b) sont en orientation opposée.19. Vector according to claim 18, characterized in that the elements (a) and (b) are in opposite orientation.
20. Vecteur selon la revendication 18 ou 19, caractérisé en ce que le promoteur inductible de l'élément (a) et le promoteur transcriptionnel de l'élément (b) sont assemblés dans le vecteur pour former un promoteur bidirectionnel régulable.20. Vector according to claim 18 or 19, characterized in that the inducible promoter of the element (a) and the transcriptional promoter of the element (b) are assembled in the vector to form a bidirectional regulatable promoter.
21. Vecteur selon la revendication 20, caractérisé en ce qu'il comprend, dans le sens 5'->3', un premier acide nucléique codant un PPAR, un premier promoteur transcriptionnel minimal contrôlant l'expression dudit premier acide nucléique, un ou plusieurs éléments de réponse à un PPAR, un deuxième promoteur transcriptionnel minimal et, sous le contrôle dudit deuxième promoteur transcriptionnel minimal, un deuxième acide nucléique codant un produit d'intérêt.21. Vector according to claim 20, characterized in that it comprises, in the 5 '-> 3' direction, a first nucleic acid encoding a PPAR, a first minimal transcriptional promoter controlling the expression of said first nucleic acid, one or several elements of response to a PPAR, a second minimum transcriptional promoter and, under the control of said second minimum transcriptional promoter, a second nucleic acid encoding a product of interest.
22. Vecteur selon l'une des revendications 18 à 21 caractérisé en ce qu'il comprend en outre un élément (d) selon la revendication 17.22. Vector according to one of claims 18 to 21 characterized in that it further comprises an element (d) according to claim 17.
23. Utilisation d'une composition selon l'une des revendications 1 à 17 ou d'un vecteur selon l'une des revendications 18 à 22 pour exprimer un acide nucléique d'intérêt dans une cellule ex vivo ou in vitro.23. Use of a composition according to one of claims 1 to 17 or of a vector according to one of claims 18 to 22 for expressing a nucleic acid of interest in a cell ex vivo or in vitro.
24. Utilisation d'une composition selon l'une des revendications 1 à 17 ou d'un vecteur selon l'une des revendications 18 à 22 pour la préparation d'un produit destiné à exprimer un acide nucléique d'intérêt dans une cellule in vivo.24. Use of a composition according to one of claims 1 to 17 or of a vector according to one of claims 18 to 22 for the preparation of a product intended to express a nucleic acid of interest in a cell in vivo.
25. Procédé pour l'expression régulée d'un acide nucléique dans une cellule, in vitro ou ex vivo, comprenant la mise en contact de ladite cellule avec une composition selon l'une des revendications 1 à 17 ou un vecteur selon l'une des revendications 18 à 22. 5125. A method for the regulated expression of a nucleic acid in a cell, in vitro or ex vivo, comprising bringing said cell into contact with a composition according to one of claims 1 to 17 or a vector according to one from claims 18 to 22. 51
26. Procédé selon la revendication 25, caractérisé en ce qu'il s'agit d'une cellule mammifère, de préférence humaine.26. The method of claim 25, characterized in that it is a mammalian cell, preferably human.
27. Procédé selon la revendication 26, caractérisé en ce qu'il s'agit d'une cellule musculaire.27. The method of claim 26, characterized in that it is a muscle cell.
28. Procédé de régulation de l'expression d'un acide nucléique in vivo comprenant l'administration d'une composition selon l'une des revendications 1 à 17 ou d'un vecteur selon l'une des revendications 18 à 22.28. A method of regulating the expression of a nucleic acid in vivo comprising the administration of a composition according to one of claims 1 to 17 or of a vector according to one of claims 18 to 22.
29. Cellule modifiée par mise en contact avec une composition selon l'une des revendications 1 à 17 ou un vecteur selon l'une des revendications 18 à 22.29. Cell modified by contacting with a composition according to one of claims 1 to 17 or a vector according to one of claims 18 to 22.
30. PPAR modifié comprenant plusieurs sites de liaison au ligand.30. Modified PPAR comprising several ligand binding sites.
31. Acide nucléique codant pour un PPAR selon la revendication 30.31. Nucleic acid encoding a PPAR according to claim 30.
32. Procédé d'identification de ligands des PPARs, comprenant la mise en contact d'une cellule selon la revendication 29 avec une molécule test et la mise en évidence d'une expression de l'acide nucléique d'intérêt.32. A method of identifying ligands for PPARs, comprising contacting a cell according to claim 29 with a test molecule and demonstrating an expression of the nucleic acid of interest.
33. Procédé d'identification de ligands des PPARs in vivo caractérisé en ce que l'on administre une composition selon l'une des revendications 1 à 17 ou un vecteur selon l'une des revendications 18 à 22 ainsi qu'une molécule test, et que l'on met en évidence une expression de l'acide nucléique d'intérêt. 33. A method of identifying ligands of PPARs in vivo, characterized in that a composition according to one of claims 1 to 17 or a vector according to one of claims 18 to 22 is administered, as well as a test molecule, and that an expression of the nucleic acid of interest is highlighted.
PCT/FR2000/001744 1999-06-22 2000-06-22 Regulation system of expression using nuclear ppar receptors WO2000078986A1 (en)

Priority Applications (12)

Application Number Priority Date Filing Date Title
JP2001505726A JP2003503034A (en) 1999-06-22 2000-06-22 Expression regulation system using nuclear PPAR receptor
CA002375869A CA2375869A1 (en) 1999-06-22 2000-06-22 Regulation system of expression using nuclear ppar receptors
KR1020017016447A KR20020028909A (en) 1999-06-22 2000-06-22 Regulation system of expression using nuclear ppar receptors
MXPA01013227A MXPA01013227A (en) 1999-06-22 2000-06-22 Regulation system of expression using nuclear ppar receptors.
HU0203584A HUP0203584A2 (en) 1999-06-22 2000-06-22 Regulation system of expression using nuclear ppar receptors
PL00353031A PL353031A1 (en) 1999-06-22 2000-06-22 Regulation system of expression using nuclear ppar receptors
AU61645/00A AU6164500A (en) 1999-06-22 2000-06-22 Regulation system of expression using nuclear ppar receptors
BR0011897-4A BR0011897A (en) 1999-06-22 2000-06-22 Composition, vector, use of a composition, processes for regulating expression of a nucleic acid in a cell, for regulating the expression of a nucleic acid and for identifying ligands of the ppar, cell, modified ppar, and, nucleic acid
IL14710400A IL147104A0 (en) 1999-06-22 2000-06-22 Regulation system of expression using nuclear ppar receptors
NZ516678A NZ516678A (en) 1999-06-22 2000-06-22 Regulation system of expression using nuclear PPAR receptors
EP00948058A EP1190084A1 (en) 1999-06-22 2000-06-22 Regulation system of expression using nuclear ppar receptors
NO20016347A NO20016347L (en) 1999-06-22 2001-12-21 Expression regulatory system using nuclear PPAR receptors and their ligands

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
FR9907957A FR2795425B1 (en) 1999-06-22 1999-06-22 PHARMACOLOGICAL REGULATION OF EXPRESSION SYSTEM USING NUCLEAR RECEPTORS BY AND THEIR LIGANDS
FR99/07957 1999-06-22
US14972199P 1999-08-20 1999-08-20
US60/149,721 1999-08-20

Publications (2)

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WO2000078986A1 WO2000078986A1 (en) 2000-12-28
WO2000078986B1 true WO2000078986B1 (en) 2001-04-19

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EP (1) EP1190084A1 (en)
JP (1) JP2003503034A (en)
KR (1) KR20020028909A (en)
CN (1) CN1370240A (en)
AU (1) AU6164500A (en)
BR (1) BR0011897A (en)
CA (1) CA2375869A1 (en)
CZ (1) CZ20014609A3 (en)
HU (1) HUP0203584A2 (en)
IL (1) IL147104A0 (en)
MX (1) MXPA01013227A (en)
NO (1) NO20016347L (en)
NZ (1) NZ516678A (en)
WO (1) WO2000078986A1 (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1263978B1 (en) * 2000-03-14 2005-12-07 Universite Pierre Et Marie Curie Inflammation-inducible hybrid promoters, vectors containing same and uses thereof
EP1288303A1 (en) * 2001-08-23 2003-03-05 Aventis Pharma S.A. Inducible expression systems employing PPAR transcriptional activators
AU2002333682A1 (en) * 2001-08-02 2003-02-17 Gencell S.A. Inducible expression systems employing ppar transcriptional activators
US10415054B2 (en) * 2013-02-04 2019-09-17 Eth Zurich Designer circuit controlling diet-induced obesity
CN107779454A (en) * 2016-08-31 2018-03-09 上海米络凯生物科技有限公司 The structure of medicaments sifting model based on PPAR γ signal paths and application

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JPH10502256A (en) * 1994-07-01 1998-03-03 ザ ソールク インスチチュート フォア バイオロジカル スタディズ Mammalian peroxisome proliferator-activated receptor and uses thereof
FR2755699B1 (en) * 1996-11-08 1998-12-18 Rhone Poulenc Rorer Sa NEW CONSTRUCTIONS AND VECTORS FOR TARGETED AND INDUCTIBLE GENE EXPRESSION

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Publication number Publication date
NO20016347L (en) 2002-02-19
CZ20014609A3 (en) 2002-05-15
BR0011897A (en) 2002-03-26
NZ516678A (en) 2004-04-30
JP2003503034A (en) 2003-01-28
CN1370240A (en) 2002-09-18
WO2000078986A1 (en) 2000-12-28
KR20020028909A (en) 2002-04-17
MXPA01013227A (en) 2002-06-04
HUP0203584A2 (en) 2003-02-28
IL147104A0 (en) 2002-08-14
AU6164500A (en) 2001-01-09
NO20016347D0 (en) 2001-12-21
EP1190084A1 (en) 2002-03-27
CA2375869A1 (en) 2000-12-28

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