Modified protein kinase A-specifc oligonucleotides and methods of their use
AssigneeHybridon, Inc., A Corporation of the State of Delaware
InventorSudhir Agrawal
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Abstract
Disclosed are synthetic, modified oligonucleotides complementary to, and capable of down-regulating the expression of, nucleic acid encoding protein kinase A subunit RIα. The modified oligonucleotides have from about 15 to about 30 nucleotides and are hybrid, inverted hybrid, or inverted chimeric oligonucleotides. Also disclosed are therapeutic compositions containing such oligonucleotides and methods of using the same.
Claims14
A method of inhibiting the proliferation of cancer cells, comprising the step of administering to the cells a synthetic, modified oligonucleotide complementary to, and capable of down-regulating the expression of, nucleic acid encoding protein kinase A subunit RIα, the modified oligonucleotide having from about 15 to about 30 nucleotides and being a hybrid, inverted hybrid, or inverted chimeric oligonucleotide,
- the hybrid oligonucleotide comprising a region of at least two deoxyribonucleotides, flanked by 3′ and 5′ flanking ribonucleotide regions each having at least four ribonucleotides,
- the inverted hybrid oligonucleotide comprising a region of at least four ribonucleotides flanked by 3′ and 5′ flanking deoxyribonucleotide regions of at least two deoxyribonucleotides, and
- the inverted chimeric oligonucleotide comprising an oligonucleotide nonionic region of at least four nucleotides flanked by two oligonucleotide phosphorothioate regions.
A method of treating cancer in an afflicted subject, comprising the step of administering to the subject a therapeutic composition comprising a synthetic, modified oligonucleotide complementary to, and capable of down-regulating the expression of, nucleic acid encoding protein kinase A subunit RIα, the modified oligonucleotide having from about 15 to about 30 nucleotides and being a hybrid, inverted hybrid, or inverted chimeric oligonucleotide,
- the hybrid oligonucleotide comprising a region of at least two deoxyribonucleotides, flanked by 3′ and 5′ flanking ribonucleotide regions each having at least four ribonucleotides,
- the inverted hybrid oligonucleotide comprising a region of at least four ribonucleotides flanked by 3′ and 5′ flanking deoxyribonucleotide regions of at least two deoxyribonucleotides, and the inverted chimeric oligonucleotide comprising an oligonucleotide nonionic region of at least four nucleotides flanked by two oligonucleotide phosphorothioate regions.
Dependencies are inferred from the claim text.