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Patent Searching and Data


Title:
PHENOTYPIC CONVERSION OF CELLS MEDIATED BY EXTERNAL GUIDE SEQUENCES
Document Type and Number:
WIPO Patent Application WO1998006440
Kind Code:
A3
Abstract:
Disclosed are a method and compositions for delivering nucleic acids to bacterial cells. The method does not require manipulation of the bacteria and is therefore particularly suited to delivery of nucleic acids to bacteria in natural environments, including inside animal bodies. The method generally involves conjugating the nucleic acid to be delivered with a cationic porphyrin and bringing the conjugate and the target bacterial cells into contact. Both the porphyrin and conjugated nucleic acid are taken up by the bacterial cells and the nucleic acid can then have a biological effect on the cells. Specifically disclosed is a method for converting drug-resistant bacterial cells to drug-sensitive cells by delivery of external guide sequences to the cells which then promote cleavage of RNA molecules involved in conferring the drug-resistant phenotype on the cells. The drug-resistant phenotype of the cells is thus converted to a drug-sensitive phenotype. The drug-sensitive cells are then susceptible to drug therapy. Also disclosed is a method and compositions for killing eukaryotic pathogens or converting drug-resistant eukaryotic cells to drug-sensitive cells. The method involves the delivery of external guide sequences, ribozymes, or vectors encoding external guide sequences or ribozymes, to eukaryotic cells. Preferred target eukaryotic cells for the disclosed method include algae, protozoa, fungi, slime mold, and cells of helminths.

Inventors:
TAKLE GARRY B
GOLDBERG ALLAN R
GEORGE SHAJI T
Application Number:
PCT/US1997/014457
Publication Date:
June 25, 1998
Filing Date:
August 15, 1997
Export Citation:
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Assignee:
INNOVIR LAB INC (US)
International Classes:
C12N15/113; A61K38/00; (IPC1-7): A61K47/48
Domestic Patent References:
WO1996021665A11996-07-18
WO1996008558A11996-03-21
WO1994012643A11994-06-09
WO1996021731A21996-07-18
WO1995027480A11995-10-19
WO1993013740A21993-07-22
WO1997033622A21997-09-18
Other References:
MERCHAT, M. ET AL.: "Meso-substituted cationic porphyrins as efficient photosensitizers of Gram-positive and Gram-negative bacteria", JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B: BIOLOGY, vol. 32, February 1996 (1996-02-01), pages 153-157, XP002052173
GUERRIER-TAKADA, C. ET AL.: "Artificial regulation of gene expression in Escherichia coli by RNase P", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA., vol. 92, November 1995 (1995-11-01), WASHINGTON US, pages 11115 - 11119, XP002052174
HIROSHI KIJIMA ET AL: "THERAPEUTIC APPLICATIONS OF RIBOZYMES", PHARMACOLOGY AND THERAPEUTICS, vol. 68, no. 2, 1995, pages 247 - 267, XP000612090
KOBAYASHI H ET AL: "Reversal of drug sensitivity in multidrug-resistant tumor cells by an MDR1 (PGY1) ribozyme.", CANCER RESEARCH, (1994 MAR 1) 54 (5) 1271-5., XP002062947
HARTMANN R K ET AL: "TOWARDS A NEW CONCEPT OF GENE INACTIVATION: SPECIFIC RNA CLEAVAGE BY ENDOGENOUS RIBONUCLEASE P", BIOTECHNOLOGY ANNUAL REVIEW, vol. 1, 1995, pages 215 - 265, XP000609333
GUERRIER-TAKADA C ET AL: "Phenotypic conversion of drug - resistant bacteria to drug sensitivity.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, (1997 AUG 5) 94 (16) 8468-72., XP002052175
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