Oligonucleotide mediated reversal of drug resistance
AssigneesHybridon, Inc., Worchester Foundation for Biomedical Research
InventorsRobert H. Barker, Jr., Eliezer Rapaport, Paul C. Zamecnik
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Abstract
The present invention provides methods of resensitizing an anti-drug-resistant infectious agent to a drug. Also disclosed are synthetic oligonucleotides having a nucleotide sequence complementary to a region of pfmdr1 nucleic acid, and methods of down-regulating the expression of pfmdr nucleic acid using such oligonucleotides.
Claims16
A synthetic oligonucleotide comprising a nucleotide sequence complementary pfmdr1 nucleic acid, wherein the nucleotide sequence is selected from the group consisting of SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, and SEQ ID NO:13.
A method of down-regulating the expression of a pfmdr1 nucleic acid comprising contacting the nucleic acid with a synthetic oligonucleotide comprising a nucleotide sequence complementary to a pfmdr1 nucleic acid, wherein the nucleotide sequence is selected from the group consisting of SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, and SEQ ID NO:13.
A method of resensitizing an anti-malarial drug-resistant Plasmodium parasite to an anti-malarial drug, comprising the steps of:
- (a) culturing the parasite in the presence of a synthetic oligonucleotide comprising a nucleotide sequence complementary to a pfmdr1 nucleic acid for a time sufficient to enable the oligonucleotide to hybridize to the nucleic acid, wherein the nucleotide sequence is selected from the group consisting of SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, and SEQ ID NO:13;
- and
- (b) contacting and culturing the parasite with an anti-malarial drug in the presence of the oligonucleotide.
A method of resensitizing a drug-resistant infectious organism to an anti-infectious organism drug, thereby reversing the drug-resistant phenotype of the organism, the method comprising the steps of:
- (a) culturing the infectious organism in the presence of a synthetic oligonucleotide comprising a nucleotide sequence complementary to a nucleic acid required for the drug-resistant phenotype for a time sufficient to enable the oligonucleotide to hybridize to the nucleic acid, wherein the nucleotide sequence is selected from the group consisting of SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, and SEQ ID NO:13;
- and
- (b) contacting and culturing the parasite with an anti-infectious organism drug in the presence of the oligonucleotide.
Dependencies are inferred from the claim text.