Gapped 2′ modified oligonucleotides
DCFirst Claim
1. A method of concurrently enhancing hybridization and RNASE H activation in a cell comprising contacting the cell with an oligonucleotide having a sequence of nucleotides which specifically hybridize to a complementary strand of nucleic acid and where at least one of the nucleotides is functionalized to increase nuclease resistance of the oligonucleotide, where a plurality of the nucleotides have a substituent group located thereon to increase binding affinity of the oligonucleotide to a complementary strand of nucleic acid, and where a plurality of the nucleotides have 2′
- -deoxy-erythro-pentofuranosyl sugar moieties.
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Abstract
Oligonucleotides and other macromolecules are provided that have increased nuclease resistance, substituent groups for increasing binding affinity to complementary strand, and sub-sequences of 2′-deoxy-erythro-pentofuranosyl nucleotides that activate RNase H enzyme. Such oligonucleotides and macromolecules are useful for diagnostics and other research purposes, for modulating protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to antisense therapeutics.
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Citations
20 Claims
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1. A method of concurrently enhancing hybridization and RNASE H activation in a cell comprising contacting the cell with an oligonucleotide having a sequence of nucleotides which specifically hybridize to a complementary strand of nucleic acid and where at least one of the nucleotides is functionalized to increase nuclease resistance of the oligonucleotide, where a plurality of the nucleotides have a substituent group located thereon to increase binding affinity of the oligonucleotide to a complementary strand of nucleic acid, and where a plurality of the nucleotides have 2′
- -deoxy-erythro-pentofuranosyl sugar moieties.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
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11. A method of modifying a sequence-specific ribonucleic acid in a cell containing RNase H and said sequence-specific ribonucleic acid comprising contacting said cell with an oligonucleotide having a sequence of nucleotides under conditions that effect hybridization of said sequence-specific ribonucleic acid and said oligonucleotide where at least one of said nucleotides is functionalized to increase nuclease resistance of the oligonucleotide, where at least one of said nucleotides has a substituent group located thereon to increase binding affinity of the oligonucleotide to a complementary strand of sequence-specific ribonucleic acid, and where a plurality of the nucleotides have 2′
- -deoxy-erythro-pentofuranosyl sugar moieties.
- View Dependent Claims (12, 13, 14, 15, 16, 17, 18, 19, 20)
Specification