Chimeric decoy
Inventors
Morishita, Ryuichi • Miyake, Takashi • Miyake, Tetsuo • Nakazawa, Takahiro • Sakaguchi, Makoto • Inoue, Satoshi • UEKI, Ryoji
Assignees
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Publication Number
US-11453880-B2
Publication Date
2022-09-27
Expiration Date
Abstract
Disclosed is a double-stranded oligonucleotide decoy including two transcription factor-binding sites, while keeping its size small. The double-stranded oligonucleotide decoy showing binding affinities for two transcription factors includes a first binding site for a first transcription factor and a second binding site for a second transcription factor. A first strand including the sense strand of the first binding site and a second strand including the sense strand of the second binding site are hybridized to form a double strand in which the sense strand of the first binding site and the sense strand of the second binding site are at least partly hybridized.
Core Innovation
The invention relates to a double-stranded oligonucleotide decoy that shows binding affinities for two transcription factors. The decoy comprises a first binding site for a first transcription factor and a second binding site for a second transcription factor, and the sense strand of the first binding site and the sense strand of the second binding site are at least partly hybridized.
The decoy is defined to have a size of 13 mer to 15 mer and is a hairpin double strand. This chimeric decoy concept places two transcription-factor binding sites in a small double-stranded oligonucleotide, with structural arrangements described as hairpin or dumbbell options.
The disclosure further characterizes chimeric combinations of transcription-factor binding sites, including NF-κB/Ets1, NF-κB/NF-AT, NF-κB/STAT1, NF-κB/STAT6, and NF-κB/NF-IL6. It also describes stabilizing modifications, including phosphorothioation for nuclease resistance, and delivery/conjugation approaches such as DDS including liposomes/peptides/atelocollagen and PLGA nanoparticles, with 5′ coupling and related linker concepts.
Claims Coverage
The independent claims (clm-00001, clm-00008, clm-00009) share a core structure: a double-stranded oligonucleotide decoy containing a first and second transcription-factor binding site in which sense strands are at least partly hybridized, providing binding affinities for two transcription factors. Across the independent claims, three main groups of inventive features are added: hairpin double strand with 13–15 mer size, phosphorothioate bonding in the decoy, and PLGA nanoparticle coupling at the 5′ end.
Two transcription-factor binding sites with partially hybridized sense strands
A double-stranded oligonucleotide decoy showing binding affinities for two transcription factors, comprising a first binding site for a first transcription factor and a second binding site for a second transcription factor, wherein a first strand comprising the sense strand of said first binding site and a second strand comprising the sense strand of said second binding site are hybridized to form a double strand in which said sense strand of the first binding site and said sense strand of the second binding site are at least partly hybridized.
Hairpin double strand decoy with 13 mer to 15 mer size
The decoy has a size of 13 mer to 15 mer and is a hairpin double strand.
Phosphorothioate bonds in the decoy
At least a part of bonds between each nucleotide in the double-stranded oligonucleotide constituting the decoy includes a phosphorothioate bond.
PLGA nanoparticle coupling at the 5′ end
The decoy has a 5′ end, and wherein the 5′ end of the decoy is bound, via a linker or directly, to a polylactic acid/glycolic acid copolymer (PLGA) nanoparticle.
Collectively, the claim set covers a chimeric double-stranded decoy that binds two transcription factors through first and second binding sites formed by sense strands that are at least partly hybridized. The coverage further includes a hairpin implementation in a 13–15 mer size range, an option requiring phosphorothioate bonds, and an option requiring 5′ end coupling of the decoy to a PLGA nanoparticle.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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