WO1996011267A1 - Adn et proteine a doigts de zinc et leur utilisation - Google Patents

Adn et proteine a doigts de zinc et leur utilisation Download PDF

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Publication number
WO1996011267A1
WO1996011267A1 PCT/DE1995/001390 DE9501390W WO9611267A1 WO 1996011267 A1 WO1996011267 A1 WO 1996011267A1 DE 9501390 W DE9501390 W DE 9501390W WO 9611267 A1 WO9611267 A1 WO 9611267A1
Authority
WO
WIPO (PCT)
Prior art keywords
dna
zinc finger
protein
finger protein
nucleotides
Prior art date
Application number
PCT/DE1995/001390
Other languages
German (de)
English (en)
Inventor
Elisabeth Schwarz
Matthias Bartelmann
Marie-Stella Reuter
Original Assignee
Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts
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 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts filed Critical Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts
Priority to JP8512260A priority Critical patent/JPH10506789A/ja
Priority to EP95935327A priority patent/EP0784680A1/fr
Publication of WO1996011267A1 publication Critical patent/WO1996011267A1/fr

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    • 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
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • Zinc finger DNA, protein and their use relates to a DNA coding for a zinc finger protein and such a protein.
  • the invention further relates to the use of the DNA and the protein.
  • the conversion of normal cells into tumor cells takes place in several steps, which involve changes in cellular genes or the acquisition of viral oncogenes. Changes in cellular genes include the activation of proto-oncogenes by mutation, gene amplification, overexpression or chromosome translocations as well as the inactivation of tumor suppressor genes by mutation or deletion.
  • genes the changes of which are important in the development of tumors, have so far been identified (cf. review article: Bishop, J.M., Cell 64 (1 991), 235-248).
  • the products of such genes have different functions. They work e.g. as transcription regulators, as links in different signal transduction chains, such as growth factors, growth factor receptors or protein kinases, or as activators or inhibitors of cell division.
  • transcription regulators are zinc finger proteins. These proteins have characteristic structures containing two cysteine and two histidine residues which are positioned relative to one another in such a way that they bind a zinc atom. Zinc finger proteins are DNA-binding proteins. An example of zinc finger proteins is the product of the Wilms tumor suppressor gene WT1, the loss of which plays an important role in the development of Wilms kidney tumors.
  • the present invention is therefore based on the object of providing a means with which tumor diagnosis and therapy can be carried out more comprehensively.
  • the invention thus relates to a DNA coding for a zinc finger protein, which comprises:
  • hybridizing DNA indicates a DNA which hybridizes with a DNA of (a) under customary conditions, in particular at 20 ° C. below the melting point of the DNA.
  • FIG. 1 shows the insert of the cDNA clone COS AP4-E1.
  • This clone comes from a cDNA library of the cervical carcinoma cell line ME 180 (cf. Reuter, M.S. et al., J. Virol. 65 (1991), 5564-5568).
  • This cell line contains the human papillomavirus 68-DNA (HPV 68-DNA) stably integrated.
  • the clone COS AP4-E1 contains HPV 68 DNA between nucleotides 1-21. It also contains cellular sequences between nucleotides 22-1476, these being exon sequences of a zinc finger gene between nucleotides 446-1476.
  • the exon sequences code for 4 zinc fingers zinc finger 1: 1130-1 191, zinc finger 2: 1214-1275, zinc finger 3: 1298-1360, zinc finger 4: 1382-1432.
  • the clone COS AP4-E1 was deposited with the DSM (German Collection of Microorganisms and Cell Cultures under DSM 9450 on September 30, 1994).
  • the above insert DNA can be part of a DNA coding for a complete zinc finger protein.
  • Such a DNA and the zinc finger protein encoded by it are thus also the subject of the invention.
  • the insert DNA from COS AP4-E1 in particular the DNA between nucleotides 446-1476
  • a cDNA library from blood cells or HeLa cells can also be used.
  • the tissues and cells mentioned contain sufficient RNA transcripts that hybridize with the insert DNA from COS AP4-E1, in particular the DNA between nucleotides 446-1476 (cf. FIG. 2). Clones obtained are subjected to sequencing and, starting from the insert DNA of COS AP4-E1, in particular the DNA between nucleotides 446-1476, the DNA coding for a zinc finger protein above is determined.
  • the insert DNA from COS AP4-E1 in particular the DNA between nucleotides 446-1476, and very particularly the DNA between nucleotides 1240-1476, is suitable for identifying a genomic DNA coding for the above zinc finger protein.
  • the corresponding DNA from COS AP4-E1 e.g. the DNA between the nucleotides 1240-1476, used as a probe for hybridizing a genomic DNA library.
  • Such can be created from the tissues and cells mentioned above.
  • the clone COS 1 APM is obtained. Its insert DNA contains in a 5.5 kb Sacl fragment the probe used, e.g. DNA corresponding to DNA between nucleotides 1240-1476. In Figures 3 and 4 this DNA from COS 1 APM is presented between nucleotides 256-492.
  • the clone COS 1 APM was deposited with the DSM under DSM 9462 on October 7, 1994. The invention thus also relates to a genomic DNA encoding the above zinc finger protein and the protein encoded by it.
  • the DNA coding for the zinc finger protein can be present in a vector or expression vector.
  • a vector or expression vector examples of such are known to the person skilled in the art.
  • these are, for example, pGE-MEX, pUC derivatives and pGEX-2T.
  • yeast for example, pY100 and Ycpadl should be mentioned, while for expression in animal cells, for example, pKCR, pEF- BOS, cDM8 and pCEV4 must be specified.
  • suitable cells in order to express the above DNA present in an expression vector examples of such cells include the E.
  • the person skilled in the art knows how the above DNA has to be inserted into an expression vector. He is also aware that the above cDNA can be expressed in E. coli, yeast or animal cells, whereas the above genomic DNA is only to be expressed in animal cells. Furthermore, the person skilled in the art knows the conditions for cultivating transformed or transfected cells. He is also familiar with methods of isolating and purifying the expressed zinc finger protein. An above, recombinantly produced zinc finger protein is therefore also the subject of the invention.
  • Another object of the invention is an antibody directed against an above zinc finger protein.
  • Such is produced in the usual way.
  • the zinc finger protein is injected subcutaneously into BALB / c mice. This injection is repeated every 3 weeks. About 2 weeks after the last injection, the serum containing the antibody is isolated and tested in the usual way.
  • the antibody is a monoclonal antibody.
  • spleen cells are removed from the mice after the fourth injection above and these are fused with myeloma cells in the usual way. The further cloning is also carried out according to known methods.
  • the present invention provides a previously unknown zinc finger DNA and a zinc finger protein encoded by it.
  • the DNA according to the invention is suitable as a probe for diagnostic purposes.
  • it can be used for gene therapy in an expression vector known to those skilled in the art.
  • the protein according to the invention is also suitable for therapeutic purposes. For this purpose, it can be administered in a customary pharmaceutical composition.
  • the present invention further provides antibodies directed against the above protein. These are ideal for diagnostic purposes.
  • the present invention thus provides new means for the diagnosis and therapy of diseases related to the DNA according to the invention and the protein encoded by them, in particular tumor diseases.
  • FIG. 2 shows the hybridization of polyA + RNA from different cells with the DNA between nucleotides 1240-1476 of COS AP4-E1
  • FIG. 3 shows a partial sequence of the genomic insert DNA of the clone COS 1
  • FIG. 4 shows the comparison of the DNA between nucleotides 1240-1476 of clone COS AP4-E1 and the DNA between nucleotides 256-
  • the invention is illustrated by the following example.
  • a ⁇ cDNA library created from HeLa cells is subjected to a conventional hybridization process.
  • the phage plaques obtained by infection of the bacteria are incubated with the 32 p-labeled DNA insert of the clone COS AP4-E1, in particular the DNA between the nucleotides 1240-1476 (cf. FIG. 1). Hybridization with individual phage plaques is obtained.
  • the phage DNA is isolated from these and cleaved with EcoRI.
  • the fragments obtained are separated electrophoretically in a 0.5% agarose gel.
  • the agarose gel is subjected to a conventional blotting process, whereby the DNA from the agarose gel is transferred to a nitrocellulose membrane.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne un ADN codant pour une protéine à doigts de zinc, ainsi qu'une telle protéine. L'invention concerne en outre l'utilisation de l'ADN et de la protéine dans le diagnostic, la thérapie ou la thérapie génétique des tumeurs. L'ADN codant pour une protéine à doigts de zinc est un insérat du clone de ADNc, COS AP4-E1. Ce clone est issu d'une bibliothèque ADNc de la lignée cellulaire du cancer du col de l'utérus ME180, qui renferme le virus du papillome humain 68-ADN et qui possède quatre doigts de zinc dans ses séquences exon.
PCT/DE1995/001390 1994-10-07 1995-10-06 Adn et proteine a doigts de zinc et leur utilisation WO1996011267A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP8512260A JPH10506789A (ja) 1994-10-07 1995-10-06 亜鉛フィンガー蛋白質をコードするｄｎａ、亜鉛フィンガー蛋白質およびそれらの使用
EP95935327A EP0784680A1 (fr) 1994-10-07 1995-10-06 Adn et proteine a doigts de zinc et leur utilisation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DEP4435919.5 1994-10-07
DE4435919A DE4435919C1 (de) 1994-10-07 1994-10-07 Zinkfinger-DNA, -Protein und ihre Verwendung

Publications (1)

Publication Number Publication Date
WO1996011267A1 true WO1996011267A1 (fr) 1996-04-18

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PCT/DE1995/001390 WO1996011267A1 (fr) 1994-10-07 1995-10-06 Adn et proteine a doigts de zinc et leur utilisation

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EP (1) EP0784680A1 (fr)
JP (1) JPH10506789A (fr)
DE (1) DE4435919C1 (fr)
WO (1) WO1996011267A1 (fr)

Cited By (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999021991A1 (fr) * 1997-10-29 1999-05-06 Shanghai Second Medical University Bmzf12: gene a doigt de zinc clone a partir de la moelle osseuse
WO1999046293A1 (fr) * 1998-03-12 1999-09-16 Shanghai Second Medical University Proteine a doigt de zinc derivee de cellules hematopoietiques
WO2001066582A1 (fr) * 2000-03-10 2001-09-13 Shanghai Biowindow Gene Development Inc. Nouveau polypeptide, proteine humaine a doigt de zinc 27, et polynucleotide codant pour ce polypeptide
WO2001066580A1 (fr) * 2000-03-07 2001-09-13 Biowindow Gene Development Inc. Shanghai Nouveau polypeptide, proteine humaine 13 a doigt de zinc, et polynucleotide codant pour ce polypeptide
WO2001066583A1 (fr) * 2000-03-10 2001-09-13 Shanghai Biowindow Gene Development Inc. Nouveau polypeptide, proteine humaine 14 a doigt de zinc, et polynucleotide codant pour ce polypeptide
WO2001068690A1 (fr) * 2000-03-15 2001-09-20 Shanghai Biowindow Gene Development Inc. Nouveau polypeptide, proteine humaine a doigt de zinc 15, et polynucleotide codant pour ce polypeptide
WO2001072803A1 (fr) * 2000-03-28 2001-10-04 Shanghai Biowindow Gene Development Inc. Nouveau polypeptide, proteine humaine a doigt de zinc 15, et polynucleotide codant pour ce polypeptide
WO2001074993A2 (fr) * 2000-03-10 2001-10-11 Shanghai Biowindow Gene Development Inc. Nouveau polypeptide, proteine humaine a doigt de zinc 17, et polynucleotide codant pour ce polypeptide
WO2001074882A1 (fr) * 2000-03-28 2001-10-11 Shanghai Biowindow Gene Development Inc. Nouveau polypeptide, proteine humaine a doigt de zinc 49, et polynucleotide codant pour ce polypeptide
WO2001074868A1 (fr) * 2000-03-07 2001-10-11 Biowindow Gene Development Inc. Shanghai Nouveau polypeptide, proteine humaine a doigt de zinc 10, et polynucleotide codant pour ce polypeptide
WO2001074865A1 (fr) * 2000-03-15 2001-10-11 Shanghai Biowindow Gene Development Inc. Nouveau polypeptide, proteine a doigt de zinc 10, et polynucleotide codant pour ce polypeptide
WO2001074866A1 (fr) * 2000-03-02 2001-10-11 Biowindow Gene Development Inc. Shanghai Nouveau polypeptide, protéine humaine a doigt de zinc 72, et polynucléotide codant pour ce polypeptide
WO2001094397A1 (fr) * 2000-06-07 2001-12-13 Shanghai Biowindow Gene Development Inc. Nouveau polypeptide, proteine a doigt de zinc 79.46, et polynucleotide codant ce polypeptide
WO2002004500A1 (fr) * 2000-06-19 2002-01-17 Biowindow Gene Development Inc. Shanghai Nouveau polypeptide, proteine humaine a doigt de zinc fpm315-17, et polynucleotide codant ce polypeptide
WO2002004502A1 (fr) * 2000-06-19 2002-01-17 Biowindow Gene Development Inc. Shanghai Nouveau polypeptide, proteine murine a doigt de zinc 16 (zfp-1), et polynucleotide codant ce polypeptide
WO2002010211A1 (fr) * 2000-06-30 2002-02-07 Shanghai Biowindow Gene Development Inc. Nouveau polypeptide, proteine humaine a doigt de zinc 12.98, et polynucleotide codant ce polypeptide
WO2002020600A1 (fr) * 2000-06-28 2002-03-14 Shanghai Biowindow Gene Development Inc. Nouveau polypeptide, proteine humaine a doigt de zinc 10.45, et polynucleotide codant ce polypeptide
US6453242B1 (en) 1999-01-12 2002-09-17 Sangamo Biosciences, Inc. Selection of sites for targeting by zinc finger proteins and methods of designing zinc finger proteins to bind to preselected sites
US6479626B1 (en) 1998-03-02 2002-11-12 Massachusetts Institute Of Technology Poly zinc finger proteins with improved linkers
US6503717B2 (en) 1999-12-06 2003-01-07 Sangamo Biosciences, Inc. Methods of using randomized libraries of zinc finger proteins for the identification of gene function
US6534261B1 (en) 1999-01-12 2003-03-18 Sangamo Biosciences, Inc. Regulation of endogenous gene expression in cells using zinc finger proteins
US6599692B1 (en) 1999-09-14 2003-07-29 Sangamo Bioscience, Inc. Functional genomics using zinc finger proteins
US6733970B2 (en) 1998-11-09 2004-05-11 Gendaq Limited Screening system for zinc finger polypeptides for a desired binding ability
US6746838B1 (en) 1997-05-23 2004-06-08 Gendaq Limited Nucleic acid binding proteins
US6790941B2 (en) 1994-01-18 2004-09-14 The Scripps Research Institute Zinc finger protein derivatives and methods therefor
US6794136B1 (en) 2000-11-20 2004-09-21 Sangamo Biosciences, Inc. Iterative optimization in the design of binding proteins
US6977154B1 (en) 1998-03-17 2005-12-20 Gendaq Limited Nucleic acid binding proteins
US7013219B2 (en) 1999-01-12 2006-03-14 Sangamo Biosciences, Inc. Regulation of endogenous gene expression in cells using zinc finger proteins
US7026462B2 (en) 2000-12-07 2006-04-11 Sangamo Biosciences, Inc. Regulation of angiogenesis with zinc finger proteins
US7030215B2 (en) 1999-03-24 2006-04-18 Sangamo Biosciences, Inc. Position dependent recognition of GNN nucleotide triplets by zinc fingers
US7067317B2 (en) 2000-12-07 2006-06-27 Sangamo Biosciences, Inc. Regulation of angiogenesis with zinc finger proteins
US7070934B2 (en) 1999-01-12 2006-07-04 Sangamo Biosciences, Inc. Ligand-controlled regulation of endogenous gene expression
USRE39229E1 (en) 1994-08-20 2006-08-08 Gendaq Limited Binding proteins for recognition of DNA
US7262054B2 (en) 2002-01-22 2007-08-28 Sangamo Biosciences, Inc. Zinc finger proteins for DNA binding and gene regulation in plants
US7273923B2 (en) 2001-01-22 2007-09-25 Sangamo Biosciences, Inc. Zinc finger proteins for DNA binding and gene regulation in plants
US7361635B2 (en) 2002-08-29 2008-04-22 Sangamo Biosciences, Inc. Simultaneous modulation of multiple genes
US7585849B2 (en) 1999-03-24 2009-09-08 Sangamo Biosciences, Inc. Position dependent recognition of GNN nucleotide triplets by zinc fingers
US7851216B2 (en) 2000-01-24 2010-12-14 Gendaq, Ltd. Methods and compositions for linking binding domains in nucleic acid binding proteins

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US7473528B2 (en) 1999-01-06 2009-01-06 Genenews Inc. Method for the detection of Chagas disease related gene transcripts in blood
WO2000040749A2 (fr) 1999-01-06 2000-07-13 Genenews Inc. Technique de detection de transcrits geniques dans le sang et leur utilisation
CN1328040A (zh) * 2000-06-12 2001-12-26 上海博德基因开发有限公司 一种新的多肽——人锌指蛋白18.04和编码这种多肽的多核苷酸
CN1331219A (zh) * 2000-06-30 2002-01-16 上海博德基因开发有限公司 一种新的多肽——人锌指蛋白18.92和编码这种多肽的多核苷酸
CN100448891C (zh) 2001-05-11 2009-01-07 安姆根有限公司 与tall-1结合的肽和相关分子
JOP20140087B1 (ar) 2013-03-13 2021-08-17 Amgen Inc بروتينات مخصصة ل baff و b7rp1 وإستخداماتها
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US6790941B2 (en) 1994-01-18 2004-09-14 The Scripps Research Institute Zinc finger protein derivatives and methods therefor
USRE42211E1 (en) 1994-08-20 2011-03-08 Gendaq, Limited Relating to binding proteins for recognition of DNA
USRE39229E1 (en) 1994-08-20 2006-08-08 Gendaq Limited Binding proteins for recognition of DNA
USRE45795E1 (en) 1994-08-20 2015-11-10 Gendaq, Ltd. Binding proteins for recognition of DNA
USRE45721E1 (en) 1994-08-20 2015-10-06 Gendaq, Ltd. Relating to binding proteins for recognition of DNA
USRE42150E1 (en) 1994-08-20 2011-02-15 Gendaq, Limited Binding proteins for recognition of DNA
US7759059B2 (en) 1997-05-23 2010-07-20 Gendaq Limited, C/O Brobeck Hale And Dorr Nucleic acid binding proteins
US6866997B1 (en) 1997-05-23 2005-03-15 Gendaq Limited Nucleic acid binding proteins
US8617807B2 (en) 1997-05-23 2013-12-31 Gendaq Limited Nucleic acid binding proteins
US7241574B2 (en) 1997-05-23 2007-07-10 Gendaq Ltd. Nucleic acid binding proteins
US6746838B1 (en) 1997-05-23 2004-06-08 Gendaq Limited Nucleic acid binding proteins
WO1999021991A1 (fr) * 1997-10-29 1999-05-06 Shanghai Second Medical University Bmzf12: gene a doigt de zinc clone a partir de la moelle osseuse
US7928195B2 (en) 1998-03-02 2011-04-19 Massachusetts Institute Of Technology Poly zinc finger proteins with improved linkers
US6479626B1 (en) 1998-03-02 2002-11-12 Massachusetts Institute Of Technology Poly zinc finger proteins with improved linkers
US7595376B2 (en) 1998-03-02 2009-09-29 Massachusetts Institute Of Technology Poly zinc finger proteins with improved linkers
US7153949B2 (en) 1998-03-02 2006-12-26 Massachusetts Institute Of Technology Nucleic acid encoding poly-zinc finger proteins with improved linkers
WO1999046293A1 (fr) * 1998-03-12 1999-09-16 Shanghai Second Medical University Proteine a doigt de zinc derivee de cellules hematopoietiques
US6977154B1 (en) 1998-03-17 2005-12-20 Gendaq Limited Nucleic acid binding proteins
US6733970B2 (en) 1998-11-09 2004-05-11 Gendaq Limited Screening system for zinc finger polypeptides for a desired binding ability
US7163824B2 (en) 1999-01-12 2007-01-16 Sangamo Biosciences, Inc. Regulation of endogenous gene expression in cells using zinc finger proteins
US6453242B1 (en) 1999-01-12 2002-09-17 Sangamo Biosciences, Inc. Selection of sites for targeting by zinc finger proteins and methods of designing zinc finger proteins to bind to preselected sites
US6534261B1 (en) 1999-01-12 2003-03-18 Sangamo Biosciences, Inc. Regulation of endogenous gene expression in cells using zinc finger proteins
US7177766B2 (en) 1999-01-12 2007-02-13 Sangamo Biosciences, Inc. Selection of sites for targeting by zinc finger proteins and methods of designing zinc finger proteins to bind to preselected sites
US6607882B1 (en) 1999-01-12 2003-08-19 Sangamo Biosciences, Inc. Regulation of endogenous gene expression in cells using zinc finger proteins
US7013219B2 (en) 1999-01-12 2006-03-14 Sangamo Biosciences, Inc. Regulation of endogenous gene expression in cells using zinc finger proteins
US7220719B2 (en) 1999-01-12 2007-05-22 Sangamo Biosciences, Inc. Modulation of endogenous gene expression in cells
US7070934B2 (en) 1999-01-12 2006-07-04 Sangamo Biosciences, Inc. Ligand-controlled regulation of endogenous gene expression
US6785613B2 (en) 1999-01-12 2004-08-31 Sangamo Biosciences, Inc. Selection of sites for targeting by zinc finger proteins and methods of designing zinc finger proteins to bind to preselected sites
US7788044B2 (en) 1999-01-12 2010-08-31 Sangamo Biosciences, Inc. Selection of sites for targeting by zinc finger proteins and methods of designing zinc finger proteins to bind to preselected sites
US7985887B2 (en) 1999-01-12 2011-07-26 Sangamo Biosciences, Inc. Regulation of endogenous gene expression in cells using zinc finger proteins
US6824978B1 (en) 1999-01-12 2004-11-30 Sangamo Biosciences, Inc. Regulation of endogenous gene expression in cells using zinc finger proteins
US8268618B2 (en) 1999-01-12 2012-09-18 Sangamo Biosciences, Inc. Repressing endogenous CCR5 gene expression in cells using engineered zinc finger proteins
US6933113B2 (en) 1999-01-12 2005-08-23 Sangamo Biosciences, Inc. Modulation of endogenous gene expression in cells
US9491934B2 (en) 1999-01-12 2016-11-15 Sangamo Biosciences, Inc. Regulation of endogenous gene expression in cells using zinc finger proteins
US6979539B2 (en) 1999-01-12 2005-12-27 Sangamo Biosciences, Inc. Regulation of endogenous gene expression in cells using zinc finger proteins
US7030215B2 (en) 1999-03-24 2006-04-18 Sangamo Biosciences, Inc. Position dependent recognition of GNN nucleotide triplets by zinc fingers
US7585849B2 (en) 1999-03-24 2009-09-08 Sangamo Biosciences, Inc. Position dependent recognition of GNN nucleotide triplets by zinc fingers
US8383766B2 (en) 1999-03-24 2013-02-26 Sangamo Biosciences, Inc. Position dependent recognition of GNN nucleotide triplets by zinc fingers
US8524874B2 (en) 1999-03-24 2013-09-03 Sangamo Biosciences Position dependent recognition of GNN nucleotide triplets by zinc fingers
US7235354B2 (en) 1999-09-14 2007-06-26 Sangamo Biosciences, Inc. Functional genomics using zinc finger proteins
US6777185B2 (en) 1999-09-14 2004-08-17 Sangamo Biosciences, Inc. Functional genomics using zinc finger proteins
US6599692B1 (en) 1999-09-14 2003-07-29 Sangamo Bioscience, Inc. Functional genomics using zinc finger proteins
US6503717B2 (en) 1999-12-06 2003-01-07 Sangamo Biosciences, Inc. Methods of using randomized libraries of zinc finger proteins for the identification of gene function
US7491531B2 (en) 1999-12-06 2009-02-17 Sangamo Biosciences, Inc. Randomized libraries of zinc finger proteins
US7943553B2 (en) 1999-12-06 2011-05-17 Sangamo Biosciences, Inc. Randomized libraries of zinc finger proteins
US7851216B2 (en) 2000-01-24 2010-12-14 Gendaq, Ltd. Methods and compositions for linking binding domains in nucleic acid binding proteins
WO2001074866A1 (fr) * 2000-03-02 2001-10-11 Biowindow Gene Development Inc. Shanghai Nouveau polypeptide, protéine humaine a doigt de zinc 72, et polynucléotide codant pour ce polypeptide
WO2001074868A1 (fr) * 2000-03-07 2001-10-11 Biowindow Gene Development Inc. Shanghai Nouveau polypeptide, proteine humaine a doigt de zinc 10, et polynucleotide codant pour ce polypeptide
WO2001066580A1 (fr) * 2000-03-07 2001-09-13 Biowindow Gene Development Inc. Shanghai Nouveau polypeptide, proteine humaine 13 a doigt de zinc, et polynucleotide codant pour ce polypeptide
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DE4435919C1 (de) 1995-12-07
JPH10506789A (ja) 1998-07-07
EP0784680A1 (fr) 1997-07-23

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