Gapped 2'-modified oligonucleotides
AssigneeIsis Pharmaceuticals, Inc.
InventorPhillip Dan Cook
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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 subsequences 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.
Claims26
An oligonucleotide comprising a sequence of nucleotide units wherein:
- at least one of said nucleotide units is functionalized to increase nuclease resistance of said oligonucleotide;
- at least one of said nucleotide units bears an aminoalkoxy, allyloxy, or imidazolylalkoxy 2'-substituent group;
- and
- a plurality of said nucleotide units have 2'-deoxy-erythro-pentofuranosyl sugar moieties, said 2'-deoxy-erythro-pentofuranosyl nucleotide units being consecutively located in said sequence of nucleotide units.
An oligonucleotide comprising a sequence of phosphorothioate nucleotides wherein:
- a plurality of said nucleotides bear an aminoalkoxy, allyloxy, or imidazolylalkoxy 2'-substituent group;
- and
- a plurality of said nucleotides have 2'-deoxy-erythro-pentofuranosyl sugar moieties.
An oligonucleotide comprising a sequence of phosphorothioate nucleotides wherein:
- a first portion of said nucleotides have 2'-deoxy-2'-fluoro, 2'-ethoxy, 2'-propoxy, 2'-aminopropoxy or 2'-allyloxy pentofuranosyl sugar moieties, and
- a further portion of said nucleotides have 2'-deoxy-erythro-pentofuranosyl sugar moieties.
An oligonucleotide comprising a sequence of nucleotide units wherein:
- at least one of said nucleotide units is functionalized to increase nuclease resistance of said oligonucleotide;
- at least one of said nucleotide units bears an aminoalkoxy 2'-substituent group;
- and
- a plurality of said nucleotide unites have 2'-deoxy-erythro-pentofuranosyl sugar moieties, said 2'-deoxy-erythro-pentofuranosyl nucleotide units being consecutively located in said sequence of nucleotide units.
Dependencies are inferred from the claim text.