Antisense oligonucleotide modulation of multidrug resistance-associated protein
AssigneeIsis Pharmaceuticals, Inc.
InventorsEdgardo Baracchini, C. Frank Bennett, Nicholas M. Dean
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Abstract
Compositions and methods are provided for the treatment and diagnosis of diseases or conditions amenable to treatment through modulation of the synthesis or metabolism of multidrug resistance-associated protein (MRP). In accordance with referred embodiments, oligonucleotides are provided which are specifically hybridizable with nucleic acids encoding MRP. In a preferred embodiment, the oligonucleotide has at least one 2'-methoxyethoxy modification. Methods of preventing the development of multidrug resistance and of improving the efficacy of chemotherapy are also disclosed.
Claims35
An oligonucleotide comprising 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein.
An oligonucleotide comprising 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein, wherein said oligonucleotide comprises at least one 2'-methoxyethoxy modification.
An oligonucleotide comprising SEQ ID NO:
- 8 and at least one 2' methoxyethoxy modification.
A method of inhibiting the synthesis of multidrug resistance-associated protein in a cell or tissue comprising contacting a cell or tissue with an oligonucleotide comprising 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of modulating the expression of multidrug resistance-associated protein.
A method of inhibiting the synthesis of multidrug resistance-associated protein in a cell or tissue comprising contacting a cell or tissue with an oligonucleotide comprising an oligonucleotide comprising SEQ ID NO:
- 8 and at least one 2' methoxyethoxy modification.
A method of treating an animal suspected of having a condition which is characterized by overexpression of multidrug resistance-associated protein comprising administering to said animal a therapeutically effective amount of an oligonucleotide having 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein.
A method for improving the efficacy of a chemotherapeutic drug treatment of a disease, said method comprising administering in conjunction with a chemotherapeutic drug treatment an oligonucleotide comprising 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein.
A method for preventing the development of multidrug resistance during a chemotherapeutic drug treatment of a disease, said method comprising administering in conjunction with a chemotherapeutic drug treatment an oligonucleotide comprising 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein.
A method of treating an animal suspected of having a condition which is characterized by leukotriene production comprising administering to said animal a therapeutically effective amount of an oligonucleotide having 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein.
Dependencies are inferred from the claim text.