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  Methods for modulating telomerase activityUSPTO Application #: 20060166864Title: Methods for modulating telomerase activity Abstract: Disclosed herein are engineered zinc finger proteins which bind to telomeric structures; methods for their design, synthesis and use; and cells comprising a telomere-binding zinc finger protein. Methods for modulating telomerase activity using telomere-binding zinc finger proteins are also provided. (end of abstract) Agent: Robins & Pasternak - Palo Alto, CA, US Inventors: Yen Choo, Mark Isalan, Sachin D. Patel, Shankar Balasubramanian, Xiohai Liu USPTO Applicaton #: 20060166864 - Class: 514006000 (USPTO) Related Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Peptide Containing (e.g., Protein, Peptones, Fibrinogen, Etc.) Doai, Heavy Metal Containing (e.g., Hemoglobin, Etc.) The Patent Description & Claims data below is from USPTO Patent Application 20060166864. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCES TO RELATED APPLICATIONS [0001] This application is a divisional application of application Ser. No. 10/271,708 filed Oct. 15, 2002, which is a continuation of application Ser. No. 09/614,679 filed Jul. 12, 2000, now U.S. Pat. No. 6,492,117, and which applications are herein incorporated by reference in their entireties. FIELD OF THE INVENTION [0002] The invention relates to DNA binding molecules. In particular the invention relates to molecules which bind to G-quadraplex or telomeric DNA. BACKGROUND OF THE INVENTION [0003] There is considerable interest in molecules that bind to telomeric DNA sequences and G-quadruplexes. Such molecules will be useful to test hypotheses of telomere length regulation, and may have therapeutic potential. [0004] Several naturally occurring proteins with affinity for G-quadruplexes have been described in the prior art (reviewed in Wellinger, R. J., & Sen, D. (1997) European Journal of Cancer 33, 735-749), although none have so far proved to be good candidates for use as diagnostic probes or therapeutic tools. [0005] Prior art quadruplex DNA binding molecules, such as recently reported DNA-binding autoantibody (Brown, B. A., Li, Y. Q., Brown, J. C., Hardin, C. C., Roberts, J. F., Pelsue, S. C., & Shultz, L. D. (1998) Biochemistry 37, 16325-16337), have only moderate binding affinities and discriminate weakly between duplex and quadruplex DNA. [0006] DNA binding molecules are disclosed in M. D. Isalan, A. Klug, and Y. Choo, International Patent Application Publication No. WO98/53057. [0007] Naturally occurring telomere-binding proteins are also unable to discriminate these structures. For example, Saccharomyces cerevisiae RAP1 (Giraldo, R., & Rhodes, D. (1994) EMBO J. 13, 2411-2420) has distinct but inseparable domains for binding quadruplexes and double stranded DNA. [0008] The present invention seeks to overcome problems associated with the prior art. SUMMARY OF THE INVENTION [0009] Disclosed herein is the engineering of DNA-binding polypeptide molecule(s) that bind to telomeric G-quadruplex structure(s). Preferably, these molecules are polypeptides comprising a zinc finger motif [0010] Zinc finger polypeptides according to the present invention advantageously bind to single stranded human telomeric DNA with an affinity comparable to the binding of naturally occurring transcription factors to their cognate duplex DNA recognition site(s). DNA in the bound complexes is preferably in the G-quadruplex conformation. [0011] Thus, in a first aspect, the invention relates to an isolated or purified molecule capable of binding to one or more of telomeric, G-quadruplex, or G-quartet nucleic acid. [0012] As used herein, the term `isolated or purified` is used to mean that a molecule is free of one or more components of its natural environment. Where the molecule(s) are produced in vitro or in vivo in a laboratory, they are considered to be isolated or purified. Isolated molecules according to the invention therefore include such molecules when produced using recombinant cell culture, phage culture etc. Molecules present in an organism expressing a recombinant nucleic acid encoding same, whether the molecule(s) are "isolated" or otherwise, are also included within the scope of the present invention. [0013] The term `molecule` has its natural meaning. Preferably, molecules according to the invention are polypeptides. [0014] The expression `capable of binding to one or more of` is used to indicate that the molecule(s) retain the ability to associate with, interact with, or bind to one or more of the mentioned entities. This binding may be reversible or irreversible. This binding may be temporary or permanent. It may be covalent, ionic, or hydrogen bonding, van-der-waals association or any other type of molecular interaction. [0015] Helomeric nucleic acid refers to nucleic acid comprised in or derived from telomeres of eukaryotic cells. The term therefore includes known telomeric repetitive DNA sequences (see below for examples), may include related RNA sequences such as telomeric primer sequences, and may include sub-telomeric repeat sequences, or other sequence(s) found at chromosome ends. The term is intended to include these nucleic acids regardless of their molecular context. This means that such molecules are included if they are in a complex with telomeric or scaffold proteins, or if they are naked in vitro. The molecules are included when they are in vivo such as bona fide telomeres in cell nuclei, or when they are removed from their natural context, such as when on a chef gel or when cloned. The term telomeric nucleic acid may also include mutants, fragments or derivatives thereof, provided such mutants, fragments or derivatives retain substantial sequence homology with said telomeric nucleic acid molecules-this is discussed in more detail below. [0016] Telomeric nucleic acids are known to adopt unconventional or non-conventional structural conformations, mediated by unusual base-pairing (i.e. other than simple base paired duplex DNA). Examples of these structures include G-quadruplexes. [0017] The term `G-quadruplex` as understood herein relates to any four-stranded DNA structure. Those skilled in the art realise that these structures comprise loops and hairpins and such like as the two strands of a duplex fold back alongside themselves to form a four-stranded structure, even though only two distinct nucleotide polymer strands may be present. It is also understood that such structures may comprise single-stranded DNA and/or double stranded DNA. Accordingly, in another aspect, the invention relates to a nucleic acid binding molecule as described above wherein said nucleic acid comprises single-stranded DNA. The feature which characterises a `G-quadruplex` as the term is used herein is that at least a part of the structure to which it refers is in a four-stranded conformation. G-quadruplexes may be intra- or inter-molecular. [0018] The term `G-quartet` refers to that part of a nucleic acid structure which is in a four-stranded conformation. A G-quartet is therefore any segment of nucleic acid or combination of nucleic acids which is in a four-stranded conformation. [0019] Thus, in another aspect, the invention relates to a nucleic acid binding molecule as described above wherein said nucleic acid is not in a double-helical conformation. [0020] Four-stranded nucleic acid conformations (ie. G-quartets) may comprise unconventional base pairing. Conventional base pairing is considered to be Watson and Crick double helical base paired nucleic acid. Unconventional base pairing is therefore base pairing other than Watson and Crick double helical base pairing. Thus, in another aspect, the invention relates to a nucleic acid binding molecule as described above wherein said nucleic acid is in a non-Watson-Crick base paired conformation. Continue reading... Full patent description for Methods for modulating telomerase activity Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Methods for modulating telomerase activity patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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