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(12) United States Patent (10) Patent No.: US 7,067,617 B2 Barbas, III Et Al

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(12) United States Patent (10) Patent No.: US 7,067,617 B2 Barbas, III Et Al US007067617B2 (12) United States Patent (10) Patent No.: US 7,067,617 B2 Barbas, III et al. (45) Date of Patent: Jun. 27, 2006 (54) ZINC FINGER BINDING DOMAINS FOR OTHER PUBLICATIONS NUCLEOTDE SEOUENCE ANN Q Nagase et al., DNA Research, 2000, vol. 7, pp. 271-281.* (75) Inventors: Carlos F. Barbas, III, Solana Beach, Zweidler-McKay, et al ... “Gifi-1 Encodes a Nuclear Zinc CA (US); Birgit Dreier, Adlikon (CH) Finger Protein That Binds DNA and Functions as a Tran s s scriptional Repressor, Mol. Cell. Biol. 16: 4024-4034 (73) Assignee: The Scripps Research Institute, La (1996). Jolla, CA (US) Dreier, et al., “Insights into the Molecular Recogntion of the s 5-GNN-3 Family of Sequences by Zinc Finger Domains’. (*) Notice: Subject to any disclaimer, the term of this J. Mol. Biol. 303: 489-502 (2000). patent is extended or adjusted under 35 Celenza, et al., “A Yeast Gene That is Essential for Release U.S.C. 154(b) by 115 days. from Glucose Repression Encodes a Protein Kinase”, Sci ence 233: 1175-1180 (1986). (21) Appl. No.: 10/080,100 Singh, et al., “Molecular Cloning of an Enhancer Binding Protein: Isolation by Screening of an Expression Library (22) Filed: Feb. 21, 2002 with a Recognition Site DNA”, Cell 52: 415-423 (1988). Kinzler, et al., “The GLI Gene is a Member of the Kruppel (65) Prior Publication Data Family of Zinc Finger Proteins”, Nature 332: 371-374 US 20O2/O165356 A1 Nov. 7, 2002 (1988). OV. f. Debs, et al., “Regulation Gene Expression in Vivo by Related U.S. Application Data Liposome-Mediated Delivery of a Purified Transcription Factor, J. Biol. Chem. 265: 10189-10192 (1990). (60) Provisional application No. 60/367,356, filed on Feb. Kudla, et al. “The Regulatory Gene areA Mediating Nitro 21, 2001. gen Metabolite Repression in Aspergillus nidulans. Muta tions Affecting Specificity of Gene Activation Alter a Loop (51) Int. Cl. Residue of a Putative Zinc Finger, EMBO.J. 9:1355-1364 C07K 9/00 (2006.01) (1990). C07K I4/00 (2006.01) Wright, et al., “Expression of a Zinc Finger Gene in HTLV (52) U.S. Cl. ....................... 530/300: 530/324; 530/350 I-and HTLV-II-Transformed Cells’, Science 248: 588-591 (58) Field of Classification Search ................ 530/300, (1990). 530/324, 350 Bergqvist, et al., “Loss of DNA-Binding and New Tran See application file for complete search history. Scriptional trans-activationFunction in Polyomavirus Large T-antigen with Mutation of Zinc Finger Motif. Nucleic (56) References Cited Acids Res. 18: 2715-2720 (1990). U.S. PATENT DOCUMENTS South, et al., “The Nucleocapsid Protein Isolated from HIV-1 Particles Binds Zinc and Forms Retroviral-Type Zinc 4,990,607 A 2, 1991 Katagiri et al. Fingers”, Biochemistry 29: 7786-7789 (1990). 5,096,815 A 3, 1992 Ladner et al. 5,223,409 A 6, 1993 Ladner et al. (Continued) 5,243,041 A 9, 1993 Fernandez-Pol 5,324,638 A 6, 1994 Tao et al. Primary Examiner Terry McKelvey 5,324.818 A 6, 1994 Nabel et al. (74) Attorney, Agent, or Firm—Catalyst Law Group. APC: 5,340,739 A 8, 1994 Stevens et al. Michael B. Farber, Esq. 5,350,840 A 9, 1994 Call et al. 5,376,530 A 12/1994 De The et al. (57) ABSTRACT 5,403.484 A 4/1995 Ladner et al. 5,597.693 A 1/1997 Evans et al. Polypeptides that contain from 2 to 12 zinc finger-nucleotide 5,639,592 A 6, 1997 Evans et al. binding regions that bind to nucleotide sequences of the 5,789,538 A 8, 1998 Rebar et al. formula (ANN)2–12 are provided. Polynucleotides that 6,140,081 A 10, 2000 Barbas encode Such polypeptides and methods of regulating gene 2002fOO81614 A1 6, 2002 Case CC expression with Such polypeptides and polynucleotides are FOREIGN PATENT DOCUMENTS also provided. WO WO95/19431 1, 1995 WO WO 96,06166 2, 1996 6 Claims, 9 Drawing Sheets US 7,067,617 B2 Page 2 OTHER PUBLICATIONS Desjarlais, et al., “Toward Rules Relating Zinc Finger Pro Rauscher, III, et al., “Binding of the Wilms Tumor Locus tein Sequences and DNA Binding Site Preferences', Natl. Zinc Finger Protein to the EGR-1 Consensus Sequence'. Acad. Sci. USA 39: 7345-7349 (1992). Science 250: 1259-1262 (1990). Hayes, et al., “Locations of Contacts between Individual Nardelli, et al., “Base Sequence Discrimination by Zinc Zinc Fingers of Xenopus laevis Transcription Factor IIIA Finger DNA-Binding Domains”, Nature 349: 175-178 and the Internal Control Region of a 5S RNA Gene'. (1991). Biochemistry 31: 11600-11605 (1992). Theisen, et al., “Amino Acid Substitutions in the SP1 Zinc Jacobs, “Determination of the Base Recognition Positions of Finger Domain Alter the DNA Binding Affinity to Cognate Zinc Fingers from Sequence Analysis, EMBO.J. 11: 4507 SP1 Target Site”, Biochem. Biophys. Res. Commun. 175: 4517 (1992). 333-338 (1991). Pabo, et al., “Transcription Factors: Structural Families and Pavletich, et al., “Zinc Finger-DNA Recognition: Crystal Principles of DNA Recognition'. Annu. Rev. Biochem. 61: Structure of a Zif268-DNA Complex at 2.1 A, Science 252: 1053-1095 (1992). 809-817 (1991). Saleh, et al., “A Novel Zinc Finger Gene on Human Chro DiBello, et al., “The Drosophila Broad-Complex Encodes a mosome 1 qter that is Alternatively Spliced in Human Family of Related Proteins Containing Zinc Fingers', Tissues and Cell Lines', Am. J. Hum. Genet. 52192-203 (1993). Genetics 129: 385-397 (1991). Hoffman, et al., “Structures of DNA-Binding Mutant Zinc Ray, et al., “Repressor to Activator Switch by Mutations in Finger Domains: Implications for DNA Binding. Protein the First Zn Finger of the Glucocorticoid Receptor: Is Direct Sci. 2:951-965 (1993). DNA Binding Necessary”, Proc. Natl. Acad. Sci. USA 88: Bellefroid, et al., “Clustered Organization of Homologous 7086-7090 (1991). KRAB Zinc-Finger Genes with enhanced Expression in Agarwal, et al., “Stimulation of Transcript Elongation Human T. Lymphoid Cells”, EMBO J. 12: 1363-1374 Requires both the Zinc Finger and RNA Polymerase II (1993). Binding Domains of Human TFIIS. Biochemistry 30: 7842 Yu, et al., “A Hairpin Ribozyme Inhibits Expression of 7851 (1991). Diverse Strains of Human Immunodeficiency Virus Type 1. Antao, et al., “A Thermodynamic Study of Unusually Stable Proc. Natl. Acad. Sci. USA 90: 6340-6344 (1993). RNA and DNA Hairpins, Nucleic Acids Res. 19: 5901-5905 Rollins, et al., “Role of TFIIIA Zinc Fingers in Vivo: (1991). Analysis of Single-Finger Function in Developing Xenopus Webster, et al., "Conversion of the EIA Cys Zinc Finger to Embryos, Mol. Cell. Biol. 13: 4776-4783 (1993). a Nonfunctional His Cys, Zinc Finger by a Single Point Julian, et al., “Replacement of His’ by Cys in a Zinc Finger Mutation, Proc. Natl. Acad. Sci, USA 88: 9989-9993 of HIV-1 NC7 Led to a Change in "H NMR-Derived 3D (1991). Structure and to a Loss of Biological Activity”, FEBS 33 1: Wilson, et al., “In Vivo Mutational Analysis of the NGFI-A 43-48 (1993). Zinc Fingers:”, J. Biol. Chem. 267:3718-3724 (1992). Pavletich, et al., “Crystal Structure of a Five-Finger GLI Thukral, et al., “Mutations in the Zinc Fingers of ADRI that DNA Complex: New Perspectives on Zinc Fingers’, Science Change the Specificity of DNA Binding and Transactiva 261: 1701-1707 (1993). tion, Mol. Cell. Biol. 12: 2784-2792 (1992). Fairall, et al., “The Crystal Structure of a Two Zinc-Finger Quigley, et al., “Complete Androgen Insensitivity Due to Peptide Reveals an Extension to the Rules for Zinc-Finger/ Deletion of Exon C of the Androgen Receptor Gene High DNA Recognition”, Nature 366: 483-487 (1993). lights the Functional Importance of the Second Zinc Finger Rebar, et al., “Zinc Finger Phage: Affinity Selection of of the Androgen in Vivo”. Mol. Endocrinol. 6: 1103-1112 Fingers with New DNA-Binding Specificities’, Science 263: (1992). 671-673 (1994). Barbas III, et al., “Semisynthetic Combinatorial Antibody Jamieson, et al., “In Vitro Selection of Zinc Fingers with Libraries: A Chemical Solution to the Diversity Problem’, Altered DNA-Binding Specificity’, Biochemistry 33: 5689 Proc. Natl. Acad. Sci. USA 89: 4457-4461 (1992). 5695 (1994). Hirst, et al., “Discrimination of DNA Response Elements for Choo, et al., “Toward a Code for the Interactions of Zinc Thyroid Hormone and Estrogen is Dependent on Dimeriza Fingers with DNA: Selection of Randomized Fingers Dis tion of Receptor DNA Binding Domains. Proc. Natl. Acad. played on Phage', Proc. Natl. Acad. Sci. USA 91: 11163 Sci. USA 89: 5527-5531 (1992). 11167 (1994). Desjarlais, et al., “Redesigning the DNA-Binding Specific Wu, et al., “Building Zinc Fingers by Selection: Toward a ity of a Zinc Finger Protein: A Data Base-Guided Therapeutic Application’. Proc. Natl. Acad. Sci. USA 92: Approach. PROTEINS: Structure, Function, and Genetics 344-348 (1995). 12: 101-104 (1992). Taylor, et al., “Designing Zinc-Finger ADRI Mutants with Nardelli, et al., “Zinc Finger-DNA Recognition: Analysis of Altered Specificity of DNA Binding to T in UAS1 Base Specificity by Site-Directed Mutagenesis'. Nucleic Sequences”, Biochemistry 34:3222-3230 (1995). Acids Res. 20: 4137-4144 (1992). Elrod-Erickson, et al., “Zif268 Protein-DNA Complex Crozatier, et al., “Single Amino Acid Exchanges in Separate Refined at 1.6 A: A Model System for Understanding Zinc Domains of the Drosophila Serendipity & Zinc Finger Pro Finger-DNA Interactions”, Structure 4: 1171-1180 (1996). tein Cause Embryonic and Sex Biased Lethality”. Genetics Jamieson, et al., “A Zinc Finger Directory for High-Affinity 131: 905-916 (1992). DNA Recognition’, Proc. Natl. Acad. Sci. USA 93: 12834 Qian, et al., “Two-Dimensional NMR Studies of the Zinc 12839 (1996).
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