US 2016/0108395 A1 · CHIMERIC SINGLE-STRANDED ANTISENSE POLYNUCLEOTIDES AND DOUBLE-STRANDED ANTISENSE AGENT

Abstract

Chimeric single-stranded polynucleotides and double-stranded antisense agents useful for modifying the expression of a target gene by means of an antisense effect are disclosed. The chimeric single-stranded antisense polynucleotide and double-stranded antisense agents comprise a central nucleotide region flanked by a first 5′-wing region and a first 3′-wing region of modified nucleotides, which are themselves flanked by a second 5′-wing region and/or a second 3′-wing region of nucleotides that have a low affinity for proteins and/or that have higher resistance to DNase or RNase than a natural DNA or RNA and are missing in a cell when the chimeric polynucleotide delivered. The double-stranded antisense agent further comprises a complementary strand annealed to the antisense strand. The polynucleotide can be used to modify RNA transcription levels, miRNA activity, or protein levels in cells.

Claims45

Dependent claims

A chimeric antisense polynucleotide comprising:

a center nucleotide region comprising at least 5 nucleotides;
a first 5′-wing region joined to the 5′ end of the center nucleotide region comprising 1-10 nucleotides wherein at least 1 is a nucleotide analog;
a first 3′-wing region joined to the 3′ end of the center nucleotide region comprising 1-10 nucleotides wherein at least 1 is a nucleotide analog;
and
a second 5′-wing region and/or a second 3′-wing region, wherein:
the second 5′-wing region is joined to the 5′ end of the first 5′-wing region and comprises at least 1 low protein-affinity nucleotide;
and
the second 3′-wing region is joined to the 3′ end of the first 3′-wing region and comprises at least 1 low protein-affinity nucleotide;
wherein the total number of nucleotides, nucleotide analogs, and low protein-affinity nucleotides is no more than 100 nucleotides.

6 more elements

Dependencies are inferred from the claim text.

Chimeric single-stranded antisense polynucleotides and double-stranded antisense agent

Life of this patent

Chimeric single-stranded antisense polynucleotides and double-stranded antisense agent

Life of this patent

Abstract

Claims45