Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1994-09-30
1997-01-28
Fleisher, Mindy
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
435 4, 435 15, 435 29, 435193, 436164, C12Q 168, C12Q 148, C12Q 102, G01N 2178
Patent
active
055976972
ABSTRACT:
The invention provides methods for the identification and discovery of agents which are inhibitors and activators of RNA and DNA-dependent nucleic acid polymerases. The essential feature of the invention is the incorporation of a functional polymerase binding site sequence (PBS) into a nucleic acid molecule which is chosen for its ability to confer a discernible characteristic via its sequence specific activity such that the incorporation of the PBS renders the nucleic acid molecule a functional template for a predetermined RNA or DNA-template directed nucleic acid polymerase (1). In the presence of the polymerase, suitable primer molecules, and any necessary accessory molecules, catalytic extension of the strand of nucleic acids complementary to the template occurs, resulting in a partial or total elimination of (or increase in) the characteristic conferring activity of the reporter-template molecule described due to the antisense effects of the complementary strand or other polymerase-mediated effects. Candidate inhibitors and activators are evaluated for their specific effects on polymerase function, versus polymerase-unrelated effects on reporter-template function, by comparing their ability to decrease or increase the extent of the characteristic conferred by the activity of the reporter-template molecule in the assay to their ability to do so in the control situation in which the activity of the polymerase has been eliminated from the assay. A novel method for controlling gene expression and, in general, the activity of a nucleic acid molecule is also disclosed.
REFERENCES:
patent: 4786600 (1988-11-01), Kramer
patent: 4876197 (1989-10-01), Burke
patent: 4880734 (1989-11-01), Burke
patent: 4912046 (1990-03-01), Henner
patent: 4957858 (1990-09-01), Chu
patent: 4980281 (1990-12-01), Housey
patent: 4994368 (1991-02-01), Goodman
patent: 5070010 (1991-12-01), Hsu
patent: 5079143 (1992-01-01), Klein
patent: 5112734 (1992-05-01), Kramer
patent: 5166057 (1992-11-01), Palese
patent: 5194370 (1993-03-01), Berninger
patent: 5215899 (1993-06-01), Dattagupta
patent: 5266464 (1993-11-01), Housey
patent: 5334525 (1994-08-01), Seeger
Ruet et al. "A Specific Assay for Yeast RNA Polymerases in Crude Cell Extracts" Eur. J. Biochem 90:325-330 1978.
Helgestrand et al. "Antiviral Screening Based Upon Cell-Free Polymerase Models and a New Selective Inhibitor" Proc. 10th Int Cong. Chemother. vol. 1 329-330 1978.
USB Catalog "GeneScribe" 127-132 1990.
Sethi "Comparison of Inhibition of Reverse Transcriptase & Antileukemic Activities Exhibited by Protoberberine & Benzophenonthridine Alcohols & Structure-Activity Relationships" Phytochem. 24(3) 447-454 1985.
Kim B. and Loeb L. A. (1995) Human Immunodeficiency Virus Reverse Transcriptase Substitutes for DNA Polymerase 1 in Escherichia coli., Proc. Nat Acad. Sci-USA 1995, Jan. 1 92(3):684-8.
Spedding G. et al (1994) A Nonradioactive Assay System for Screening for Inhibitors of Reverse Transcriptase Trends in Genetics (10) 11:388-389 Nov. 1994.
Goff et al (1981) Isolation and properties of Moloney murine leukemia virus mutants: use of a rapid assay for release of virion reverse transcriptase, Journal of Virology, 38, 239-248 Aug. 1992.
Huang et al (1990) Selective action of 3'-Azido-3'-deoxythymidine 5'-Triphosphate on viral reverse transcriptase and human DNA polymerases, The Journal of Biological Chemistry, 265, 11914-11918 Jul. 1990.
Orr et al (1992) DNA chain termination activity and inhibition of human immunodeficiency virus reverse transcriptase by carbocyclic 2', 3'-dihydro-2', 3'-dideoxyguanosine triphosphate, The Journal of Biological Chemistry, 267, 4177-4182 Feb. 1992.
Murray and Crocket, "Antisense Techniques: An Overview" in Antisense RNA and DNA, J. A. H. Murray, ed., Wiley-Liss Inc., 1-49 (1992).
Weiss et al. (1992) Synthetic human tRNA.sup.Lys3 and natural bovine tRNA.sup.Lys3 interact with HIV-1 reverse transcriptase and serve as specific primers for retroviral cDNA synthesis, Gene, 111, 183-197 Feb. 1992.
Wang and Seeger (1992) The reverse transcriptase of Hepatitis B Virus acts as a protein primer for viral DNA synthesis, Cell, 71, 663-670 Nov., 1992.
Gossen and Bujard (1992) Tight control of gene expression by tetracycline-responsive promoters, Proc. Natl. Acad. Sci. USA, 89, 5547-5551 Jun. 1992.
Kohlstaedt and Steitz (1992) Reverse transcriptase of human immunodeficiencey virus can use either human tRNA3.sup.Lys or Escherichia coli tRNA2.sup.Gln as a primer in an in vitro primer-utilization assay, Proc. Natl. Acad. Sci. USA 89, 9652-9656 Oct. 1992.
Parvin and Sharp (1993) DNA topology and a minimal set of basal factors for transcription by RNA Polymerase II, Cell 73, 533-540 May 1993.
Degen Nancy J.
Fleisher Mindy
LandOfFree
Screening assay for inhibitors and activators of RNA and DNA-dep does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Screening assay for inhibitors and activators of RNA and DNA-dep, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Screening assay for inhibitors and activators of RNA and DNA-dep will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-940765