RNA polymerase II peptides and methods of use

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

514 2, 514 12, 514 17, 435194, 530329, 530402, A61K 3800, A61K 3804, A01N 3718, C12N 912

Patent

active

060907843

ABSTRACT:
A macromolecular delivery method that utilizes a series of peptides with unique and versatile nuclear targeting properties has been developed, where the peptides are derived from the COOH terminal domain (CTD) of the largest subunit of RNA polymerase II and include heptapeptide units similar or identical to the following consensus sequence: Tyrosine--Serine--Proline--Threonine--Serine--Proline--Serine (YSPTSPS).sub.x (SEQ ID NO. 1). When expressed in vivo, the CTD peptides are phosphorylated and they accumulate in discrete compartments within the nucleus. The CTD peptides concentrate indicator molecules in discrete subnuclear compartments where pre-mRNA molecules are synthesized and spliced. The length and composition of the CTD peptides can be manipulated to obtain different intranuclear partitioning properties. The CTD peptides are functional in the nuclei of S. cerevisiae, S. pombe, nematodes, insects, plants, and all vertebrates. Since the CTD peptides accumulate precisely in discrete sites inhabited by RNA polymerase II and the spliceosomes, they should be useful in genetic therapy technologies.

REFERENCES:
patent: 4244946 (1981-01-01), Rivier et al.
patent: 4305872 (1981-12-01), Johnston et al.
patent: 4316891 (1982-02-01), Guillemin et al.
patent: 4629784 (1986-12-01), Stammer
patent: 4792525 (1988-12-01), Ruoslahti et al.
patent: 5565327 (1996-10-01), Greenleaf et al.
Allison et al., Mol. Cell. Biol., Jan. 1988, 8(1): 321-329.
Allison et al., Cell, vol. 42: 599-610, 1985.
Agrawal, et al., "Drug Disposition--Pharmocokinetics of Antisense Oligonucleotides," Clin. Pharmacokinetics 28, 7-16 (1995).
Agrawal and Akhtar, "Advances in Antisense Efficacy and Delivery," Trends in Biotechnol., 13, 197-199 (1995).
Agrawal, et al., "Modified Oligonucleotides as Therapeutic and Diagnostic Agents," Current Opinion in Biotechnol. 6(1), 12-19 (1995).
Ahearn et al., "Cloning and Sequence Analysis of the Mouse Genomic Locus Encoding the Largest Subunit of RNA Polymerase, II," J. Biol. Chem. 262, 10695-10705 (1987).
Akoulitchev, et al., "Requirement for TFIIH Kinase Activity in Transcription by RNA Polymerase, II," Nature 377, 557-660 (1995).
Allison, et al., "The C-Terminal Domain of the Largest Subunit of RNA Polymerase II of Saccharomyces Cervisiae, Drosophila Melanogaster, and Mamals: A Conserved Structure with an Essential Function," Molecular and Cellular Biology, 8(1), 321-329 (1988).
Altman, et al., "Recent Studies of Ribonuclease P," Faseb J. 7(1), 7-14 (1993).
Altman, "Commentary--RNA Enzyme-Directed Gene Therapy," Proc. Natl. Acad. Sci. USA 90(23), 10898-10900 (1993).
Barinaga, "Ribozymes: Killing the Messenger," Science 262, 1512-1514 (1993).
Baron, Andre et al., "Localization of the Centrin-Related 165,000-M.sub.1 Protein of PtK.sub.2 Cells During the Cell Cycle," Cell Motil. and the Cytoskel. 18, 1-14 (1991).
Bartolomei et al, "Genetic Analysis of the Repetitive Carboxyl-Terminal Domain of the Largest Subunit of Mouse RNA Polymerase II," Mol. Cell. Biol., 8, 330-339 (1988).
Biggs et al., "Structure of the Eukaryotic Transcription Apparatus: Features of the Gene for the Largest Subunit of Drosophila RNA Polymerase II," Cell 42, 611-621 (1985).
Bird and Riddle, "Molecular Cloning and Sequencing of ama-I, the Gene Encoding the Largest Subunit of Caenorhabditis elegans RNA Polymerase II," Mol. Cell. Biol. 9, 4119-4130 (1989).
Corden et al., "A Unique Structure at the Carboxyl Terminus of the Largest Subunit of Eukaryotic RNA Polymerase II," Proc. Natl. Acad. Sci. USA 82, 7934-7938 (1985).
Crooke, "Oligonucleotide Therapeutics: A Prospectus," Antisense Res. Develop. 3, 1-2 (1993).
Crystal, "Transfer of Genes to Humans: Early Lessons and Obstacles to Success," Science 270, 404-410 (1995).
De Clercq, "Antiviral Therapy for Human Immonodeficiency Virus Infections," Clin. Microbiol. Rev. 8, 200-239 (1995).
Dietrich et al., "Analysis of the Genes Encoding the Largest Subunit of RNA Polymerase II in Arabidopsis and Soybean," Plant Mol. Biol. 15, 207-223 (1990).
Evers et al., "Trypanosoma Brucei Contains Two RNA Polylmerase II Largest Subunit Genes with an Altered C-Terminal Domain," Cell 56, 585-597 (1989).
Feaver et al, "Relationship of CDK-Activating Kinase and RNA Polymerase II CTD Kinase TFIIH/TFIIK," Cell 79, 1103-1109 (1994).
Harding, "NMR Studies YSPTSPSY: Implications for the Design of DNA Bisintercalators," Journal of Medicicnal Chemistry, 35, 4658-4664 (1992).
Herrmann, "Cancer Gene Therapy: Principles, Problems, and Perspectives," J. Molec. Med. 73, 157-163 (1995).
Jokerst et al., "Analysis of the Gene Encoding the Largest Subunit of RNA Polymerase II in Drosophila," Mol. Gen. Genet. 215, 266-275 (1989).
Khiat, et al., "Structural Differences Between the Free and Bound States of DNA-Bisintercalating Peptide YSPTSPSY," Journal of Medicinal Chemistry, 39(21), pp. 2492-2498 (1996).
Koleske, et al., "The RNA Polymerase II Holoenzyme and Its Implications for Gene Regulation," Trends in Biochemical Sciences, 20, 113-116 (1995).
Liu and Altman, "Inhibition of Viral Gene Expression by the Catalytic RNA Subunit of RNase P from Escherichia coli," Genes & Devel. 9(4), 471-480 (1995).
Merrifield J., "Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide," J. Am. Chem. Soc. 85, 2149-2154 (1964).
Miller, "Human Gene Therapy Comes with Age," Nature 357, 455-460 (1992).
Mulligan, "The Basic Science of Gene Therapy," Science 260, 926-932 (1993).
Price and Pettijohn, "Redistribution of the Nuclear Mitotic Apparatus Protein (NuMA) during Mitosis and Nuclear Assembly--Properties of Purified NuMA Protein," Exp. Cell Res. 166, 295-311 (1986).
Roy et al, "The MO15 Cell Cycle Kinase is Associated with the TFIIH Transcription-DNA Repair Factor," Cell 79, 1093-1101 (1994).
Sambrook, Frisch & Maniatis, Molecular Cloning: A Laboratory Manual, 2nd Ed., (Cold Spring Harbor Laboratory, NY 1989), "Table of Contents."
Seipel, et al., "Basal Components of the Transcription Apparatus (RNA Polymerase II, TATA-binding Protein) Contain Activation Domains: Is Repetitive C-Terminal Domain (CTD) of RNA Polymerase II a Portable Enhancer Domain?," Chemical Abstracts, 122(17), Abstract No. 206769 (1944).
Sullenger and Cech, "Tethering Ribozymes to a Retroviral Packaging Signal for Destruction of Viral RNA," Science 262, 1566-1569 (1993).
Temsamani, et al., "Cellular Uptake of Oligodeoxynucleotide Phosphorothioates and Their Analogs," Antisense Res. & Devel. 4, 35-42 (1994).
Wagner, "Gene Inhibition Using Antisense Oligodeoxynucleotides," Nature 372, 333-335 (1994).
Warren, et al., "Coordinated Transcription-Dependent Redistribution," Journal of Cellular Biochemistry, Supplement 21B, p.141 (1995).
Warren and Nelson, "Nonmitogenic Morphoregulatory Action of pp60.sup.v-src on Multicellular Epithelial Structures," Mol. Cell. Biol. 7, 1326-1337 (1987).
Winzerith et al., "Complete Sequence of the Human RNA Polymerase II Largest Subunit," Nucleic Acids Research 20, 910 (1992).
Yang et al., "NuMA: An Unusually Long Coiled-Coil Related Protein in the Mammalian Nucleas," J. Cell Biol. 116, 1303-1317 (1992).
Yu, et al., "A Hairpin Ribozyme Inhibits Expression of Diverse Strains of Human Immuodeficiency Virus Type I," Proc. Natl. Acad. Sci. USA 90, 6340-6344 (1993).
Yuan, et al., "Targeted Cleavage of mRNA by Human RNase P," Proc. Natl. Acad. Sci. USA 89(17), 8006-8010 (1992).
Zamecnik, et al., "Oligodeoxynucleotide Hybridization Inhibition of HIV and Influenza Virus," Nucleic Acids Symp. Series 24, 127-131 (1991).

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

RNA polymerase II peptides and methods of use does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with RNA polymerase II peptides and methods of use, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and RNA polymerase II peptides and methods of use will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-2037161

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.