Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1994-02-22
1997-09-30
Chambers, Jasemine C.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
435 5, 435 911, 536 253, C12Q 170, C12Q 168, C07H 2100, C12P 1934
Patent
active
056724721
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to the development of drugs and of biologically active diagnostics and research reagents. In particular, this invention relates to the synthetic unrandomization of oligomer fragments to determine fragments specifically active for target molecules.
BACKGROUND OF THE INVENTION
Oligomers may be designed which are useful for therapeutic, diagnostic and research applications. In the past, development of biologically active oligomer substances was often limited to the modification of known sequences, unit by unit, until a desired Characteristic or efficacy was achieved. However, in addition to time drawbacks, protocols employing these types of methodologies are limiting in that the final product is based upon, and often not far removed from, the structure of the starting material.
Recently, new methods have been developed whereby drugs and biologically active substances can be "designed." A variety of combinatorial strategies have been described to identify active peptides. Houghton, et al. Nature 1991, 354, 84; Lam, et al., Nature 1991, 354, 82; Owens, et al., Biochem. Biophys. Res. Commun. 1991, 181, 402; Fodor, et al., Science 1991, 251, 767; Geysen, et al., Molecular Immunology 1986, 23, 709; Zuckermann, et al., Proc. Natl. Acad. Sci. 1992, 89, 4505; Rutter, et al., U.S. Pat. No. 5,010,175 issued Apr. 23, 1991.
Focusing on the field of nucleic acid-protein binding, combinatorial nucleic acid selection methods generally select for a specific nucleic acid sequence from a pool of random nucleic acid sequences based on the ability of selected sequences to bind to a target protein. The selected sequences are then commonly amplified and the selection process repeated until a few strong binding sequences are identified. These methods generally employ enzymatic steps within the protocol. Commonly T7 RNA polymerase and Taq I associated with polymerase chain reaction amplification methods are employed. One group recently identified a target sequence to the RNA-binding protein gp43. Tuerk and Gold, Science 1990 249, 505. Tuerk and Gold's "systematic evolution of ligands by exponential enrichment" (SELEX) method identified specifically bindable RNA sequences using four cycles of amplification of RNA sequences having variable portions therein and which were specifically bindable to gp43.
Another group designed DNA molecules which recognized the protease thrombin. Bock, et al., Nature 1992, 355, 564. This method involves the preparation of a population involving a random region flanked by known primer regions followed by PCR amplification and selection. Small molecule mimics of metabolic cofactors have been selectively recognized by RNA sequences in this manner by Ellington and Szostak, Nature 1990, 346, 818. These techniques were suggested to be useful to design oligonucleotide ligands, however their dependence upon enzymatic means for amplification and sequence determination limits their uses. Simpler methods for the identification of useful oligomers which are specifically bindable to target molecules and which express specific activity for target molecules are greatly desired. Methods which are not dependent upon enzymatic means would simplify protocols as well as expand the range of substrates with which the protocols would be effective. For example, presently there are over one hundred nucleotide analogs available. Cook, P. D., Anti-Cancer Drug Design 1991, 6, 585 and Uhlmann, et al., Chem. Rev. 1990, 90, 544. Since not all analogs are amenable to enzymatic processes, a non-enzymatic means for determining useful oligomer sequences which are specifically bindable to target sequences is greatly desired. Such methods could determine oligomers which are specifically bindable, not only to natural RNA-binding proteins, but also to any protein, nucleic acid, or other target molecule.
Methods are also greatly desired for determining useful oligomer sequences having particular desired activity, not limited to binding of target molecules. Such activity may include, but is not
REFERENCES:
patent: 4833092 (1989-05-01), Geysen
patent: 5010175 (1991-04-01), Rutter et al.
patent: 5194392 (1993-03-01), Geysen
Fodor et al., Light-Directed, Spatially Addressable Parallel Chemical Synthesis Science 1991 251:767-773.
Riordan et al. (1991 Apr) "Oligonucleotide-Based Therapeutics" Nature 350: 442-443.
Sullenger et al. (1990) "Overexpression of TAR Sequences Renders Cells Resistant to Human Immunodeficiency Virus Replication" Cell 63:601-608.
Vickers et al., "Inhibition of HIV-LTR Gene Expression By Oligonucleotides Targeted to the TAR Element" Nuc. Acids. Res. 19: 3359-3368 (1991).
Mason et al., "Diversity of the Antibody Response" Vaccines 86: 97-103 (1986).
Geysen et al., "Strategies for Epitope Analysis Using Peptide Synthesis", J. Immunol Meth. 102: 259-274 (1987).
Van Der Zee et al., "Efficient Mapping and Characterization of a T Cell Epitope by the Simultaneous Synthesis of Multiple Peptides", Characterization Eur. J. Immunol 19: 43-47 (1989).
Vickers et al., Abstract only Nucleic Acids. Res. 19: 3359-3368 (1991).
Houghten et al., "Generation and Use of Synthetic Peptide Combinatorial Libraries for Basic Research and Drug Discovery", Nature 354: 84-86 (1991).
Tuerk and Gold, "Systematic Evolution of Ligands by Exponential Enrichment: RNA Ligands to Bacteriophage T4 DNA Polymerase", Science 249: 505-510 (1990).
Ellington and Szostak, "In Vitro Selection of RNA Molecules That Bind Specific Ligands", Nature 346: 818-822 (1990).
Yamada, "Adhesive Recognition Sequences", J. Biol. Chem. 266: 12809-12812 (1991).
Dustin and Springer, "Lymphocyte Function-Associated Antigen-1 (LFA-1) Interaction Adhesion Molecule-1 (ICAM-1) is One of At Least Three Mechanisms for Lymphocyte Adhesion to Cultured Endothelial Cells", J. Cell. Biol. 107: 321-331 (1988).
Bock et al., "Selection of Single-Stranded DNA Molecules That Bind and Inhibit Human Thrombin" Nature 355: 564-566 (1992).
Green et al., "In Vitro Genetic Analysis of the Tetrahymena Self-Splicing Intron", Nature 347: 406-408 (1990).
Robertson and Joyce, "Selection In Vitro of an RNA Enzyme that Specifically Cleaves Single-Stranded DNA", Nature 344: 467-468 (1990).
Joyce, "Amplification, Mutation and Selection of Catalytic RNA", Gene 82: 83-87 (1989).
Chittenden et al., "The T/E1A-Binding Domain of the Retinoblastoma Product Can Interact Selectively With a Sequence-Specific DNA-Binding Protein", Cell 65: 1073-1082 (1991).
Kinzler and Vogelstein, "The GLI Gene Encodes a Nuclear Protein Which Binds Specific Sequences in the Human Genome", Molec. Cell. Biol. 10: 634-642 (1990).
Thiesen and Bach, "Target Detection Assay (TDA) : A Versatile Procedure to Determine DNA Binding Sites as Demonstrated On SP1 Protein", Nucleic Acid Research 18: 3203-3209 (1990).
Kinzler and Vogelstein, "Whole Genome PCR: Application to the Indentification of Sequences Bound by Gene Regulatory Proteins", Nucleic Acid Research 17: 3645-3653 (1989).
Blackwell and Weintraub, "Differences and Similarities in DNA-Binding Preferences of MyoD and E2A Protein Complexes Revealed by Binding Site Selection", Science 250: 1104-1110 (1990).
Blackwell et al, "Sequence-Specific DNA Binding by the c-Mye Protein", Science 250: 1149-1151 (1990).
Geysen et al, "A Priori Delineation of a Peptide Which Mimics a Discontinuous Antigenic Determinant", Molecular Immunology 23: 709-715 (1986).
Ecker et al., "Rational Screening of Oligonucleotide Combinatorial Libraries for Drug Discovery", Nuc. Acids Res 21: 1853-1856 (1993).
Wyatt et al., "Combinatorially Selected Guanosine-Quartet Structure is a Potent Inhibitor of Human Immunodeficiency Virus Envelope-Mediated Cell Fusion".
Anderson Kevin
Bruice Thomas W.
Davis Peter
Ecker David J.
Hanecak Ronnie C.
Chambers Jasemine C.
ISIS Pharmaceuticals Inc.
Priebe Scott D.
LandOfFree
Synthetic unrandomization of oligomer fragments does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Synthetic unrandomization of oligomer fragments, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Synthetic unrandomization of oligomer fragments will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2255916