Chemistry: molecular biology and microbiology – Vector – per se
Patent
1995-05-02
1999-03-02
Elliott, George C.
Chemistry: molecular biology and microbiology
Vector, per se
435325, 435243, 536 232, 536 235, 536 2372, 536 241, C12N 1563, C12N 510, C12N 100, C12N 1511
Patent
active
058770100
ABSTRACT:
The present invention provides isolated nucleic acid molecules encoding a Herpesviridae thymidine kinase enzyme comprising one or more mutations, at least one of the mutations encoding an amino acid substitution upstream from a DRH nucleoside binding site which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase. Within another aspect, one of the mutations is an amino acid substitution within a DRH nucleoside binding site which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase. Also provided are vectors suitable for expressing such DNA molecules, as well as methods for utilizing such vectors.
REFERENCES:
patent: 5288641 (1994-02-01), Roizman
patent: 5401835 (1995-03-01), Chishti
Orkin et al. Report and recommendations of the panel to assess the NIH investment in research on gene theapy, Dec. 7, 1995.
Karkas et al. Stereochemical consideration in the enxymatic phosphorylation and antiviral activity of acyclonucleosides. I. Phosphorylation of 2'-nor-2'deoxyguanosine Biochem. Biophys. Acta vol. 911 127-135, 1987.
Sasaoka et al. Analysis of the human tyrosine hydroxylase promoter-chloramphenicol acetyltransferase chimeric gene expression in transgenic mice Molecular Brain Res. vol. 16 274-286, 1992.
Borelli et al. Targeting of an inducible toxic phenotype in animal cells Proc. Natl. Acad. Sci. USA vol. 85 7572-7576, 1988.
Culver et al. In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors Science vol. 256 1550-1552, 1992.
Black and Loeb, "Identification of Important Residues within the Putative Nucleoside Binding Site of HSV-1 Thymidine Kinase by Random Sequence Selection: Analysis of Selected Mutants in Vitro," Biochemistry 32: 11618-11626, 1993.
Dube and Loeb, "Mutants Generated by the Insertion of Random Oligonucleotides into the Active Site of the .beta.-Lactamase Gene," Biochemistry 28:5703-5707, 1989.
Dube et al., "Artificial Mutants Generated by the Insertion of Random Oligonucleotides into the Putative Nucleoside Binding Site of the HSV-1 Thymidine Kinase Gene," Biochemistry 30: 11760-11767, 1991.
Munir et al., "Herpes thymidine kinase mutants with altered catalytic efficiencies obtained by random sequence selection," Protein Engineering 7(1):83-89, 1994.
Munir et al., "Permissible Amino Acid Substitutions within the Putative Nucleoside-binding Site of Herpes Simplex Virus Type 1 Encoded Thymidine Kinase Established by Random Sequence Mutagenesis," Journal of Biological Chemistry 267(10):6584-6589, 1992.
Munir et al., "Thymidine kinase mutants obtained by random sequence selection," Proc. Natl. Acad. Sci. USA 90: 4012-4016, 1993.
Balasubramaniam et al., "Herpesviral deoxythymidine kinases contain a site analogous to the phosphoryl-binding argininie-rich region of porcine adenylate kinase; comparison of secondary structure predictions and conversation," Journal of General Virology 71: 2979-2987, 1990.
Barba et al., "Thymidine kinase-mediated killing of rat brain tumors," Journal of Neurosurgery 79: 729-735, 1993.
Caruso et al., "Regression of established macroscopic liver metastases after in situ transduction of a suicide gene," Proc. Natl. Acad. Sci. USA 90: 7024-7028, 1993.
Czako and Marton, "The Herpes Simplex Virus Thymidine Kinase Gene as a Conditional Negative-Selection Marker Gene in Arabidopsis thaliana," Plant Physiol. 104: 1067-1071, 1994.
Darby et al., "Evidence that the `Active Centre`of the Herpes Simplex Virus Thymidine Kinase Involves an Interaction between Three Distinct Regions of the Polypeptide," Journal. gen. Virol. 67:753-758, 1986.
Drinkwater and Klinedinst, "Chemically induced mutagenesis in a shuttle vector with a low-background mutant frequency," Proc. Natl. Acad. Sci. USA 83:3402-3406, 1986.
Dube et al., "The association of thymidine kinase activity and thymidine transport in Escherichia coli," Gene 99: 25-29, 1991.
Fetzer et al., "Site-Directed Mutagenesis in the Active Site of the Herpes Simplex Virus Type 1 Thymidine Kinase Gene," Virus Genes 7(2):205-209, 1993.
Gentry, G., "Viral Thymidine Kinases and Their Relatives," Pharmac. Ther. 54:319-355, 1992.
Hardy et al., "Atomic Structure of Thymidylate Synthase: Target for Rational Drug Design," Science 235: 448-455, 1987.
Horwitz and Loeb, "DNA Sequences of Random Origin as Probes of Escherichia coli Promoter Architecture," Journal of Biological Chemistry 236(29): 14724-14731, 1988.
Horwitz and Loeb, "Promoters selected from random DNA sequences," Proc. Natl. Acad. Sci. USA 83: 7405-7409, 1986.
Horwitz et al., "Selection of new biological activities from random nucleotide sequences: evolutionary and practical considerations," Genome 31: 112-117, 1989.
Kit et al., "Nucleotide Sequence Changes in Thymidine Kinase Gene of Herpes Simplex Virus Type 2 Clones from an Isolate of a Patient Treated with Acyclovir," Antimicrobial Agents and Chemotherapy 31(10): 1483-1490, 1987.
Knoll et al., "Mapping of the active site of T7 RNA polymerase with 8-azido ATP," Biochimica et Biophysica Acta 1121: 252-260, 1992.
Konrad, M., "Cloning and Expression of the Essential Gene for Guanylate Kinase from Yeast," Journal of Biological Chemistry 267(36): 25652-25655, 1992.
Koonin and Senkevich, "Evolution of Thymidine and Thymidylate Kinases: The Possibility of Independent Capture of TK Genes by Different Groups of Viruses," Virus Genes 6(2): 187-196, 1992.
Liao and Wise, "A simple high-efficiency method for random mutagensis of cloned genes using forced nucleotide misincorportion," Gene 88(1): 107-111, 1990.
McKnight, S., "The nucleotide sequence and transcript map of the herpes simplex virus thymidine kinase gene," Nucleic Acids Research 8(24):5949-5964, 1980.
Miller and Miller, "Phosphorylation of Acyclovir (Acycloguanosine) Monophosphate by GMP Kinase," Journal of Biological Chemistry 225(15):7204-7207, 1980.
Montfort et al., "Structure, Multiple Site Binding, and Segmental Accommodation in Thymidylate Synthase on Binding dUMP and an Anti-Folate," Biochemistry 29(30): 6964-6977, 1990.
Moolten et al., "Lymphoma Regression Induced by Ganciclovir in Mice Bearing a Herpes Thymidine Kinase Transgene," Human Gene Therapy 1: 125-134, 1990.
Moolten et al., "Multiple transduction as a means of preserving ganciclovir chemosensitivity in sarcoma cells carrying retrovirally transduced herpes thymidine kinase genes," Cancer Letters 64: 257-263, 1992.
Panicali and Paoletti, "Construction of poxviruses as cloning vectors: Insertion of the thymidine kinase gene from herpes simplex virus into the DNA of infectious vaccinia virus," Proc. Natl. Acad. Sci. USA 79: 4927-4931, 1982.
Ram et al., "In Situ Retroviral-mediated Gene Transfer for the Treatment of Brain Tumors in Rats," Cancer Research 53: 83-88, 1993.
Ram et al., "Toxicity studies of retroviral-mediated gene transfer for the treatment of brain tumors," Journal of Neurosurgery 79: 400-407, 1993.
Roberts et al., "Mutant Varicella-Zoster Virus Thymidine Kinase: Correlation of Clinical Resistance and Enzyme Impairment," Journal of Virology 65(12): 6407-6413, 1991.
Rosenberg et al., "Observations on the Systemic Administration of Autologous Lymphokine-Activated Killer Cells and Recombinant Interleukin-2 to Patients With Metastatic Cancer," New England Journal of Medicine 313(23): 1485-1492, 1985.
Sanderson et al., "Purification and Crystallization of Thymidine Kinase from Herpes Simplex Virus Type 1," J. Mol. Biol. 202(4): 917-919, 1988.
Sawyer et al., "Molecular Analysis of the Pyrimidine Deoxyribonucleoside Kinase Gene of Wild-type and Acyclovir-resistant Strains of Varicella-Zoster Virus," J. gen. Virol. 69: 2585-2593, 1988.
Suzutani et al., "Kinetic studies of the predicted substracte-binding site of varicella-zoster virus thymidine kinase," Journal of General Virology 74: 1011-1016, 1993.
Suzutani et al., "Random Mutagenesis of the Thymidine Kinase Gene of Varicella-Zoster Virus," Journal of Virology 66(4): 2118-2124, 1992.
Takamiya et al., "Gene Therapy of Malignant Brain Tumors: A Rat Glioma Line Bearing the Herpes Simplex Virus Type 1
Black Margaret E.
Loeb Lawrence A.
Brusca John S.
Elliott George C.
University of Washington
LandOfFree
Thymidine kinase mutants does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Thymidine kinase mutants, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Thymidine kinase mutants will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-421889