The present invention relates to a polynucleotide comprising a Nuclear factor of activated T-cells (NFAT) binding site sequence and a reverse complement of said NFAT binding site sequence separated by a spacer sequence, to said polynucleotide for use in treating and/or preventing disease, and to viral particles, compositions, and uses related thereto. The present invention further relates to a polynucleotide comprising a Nuclear factor of activated T-cells (NFAT) binding site sequence and a reverse complement of said NFAT binding site sequence for use in treating and/or preventing an NFAT-mediated disease.

This application pertains to a hairpin nucleic acid molecule capable of modulating expression of a target gene and a use thereof. A nucleic acid molecule according to an embodiment can modulate expression of a target gene in a specific manner for cells in which a miRNA hybridizable therewith is present, finding advantageous applications in compositions for regulating expression of a target gene or pharmaceutical compositions for treating diseases.

The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

An RNA and protein delivery system utilizing an RNA-protein complex having a higher-order structure, and an RNA-protein complex having a novel higher-order structure.

An isolated oligonucleotide comprising ribonucleotides is disclosed. The oligonucleotide comprises a nucleic acid sequence which encodes at least one copy of a splicing-factor binding site. The oligonucleotide is no more than 150 bases and may be devoid of a sequence that allows hybridization thereof to cellular RNA under physiological conditions. The oligonucleotide inhibits overall cellular splicing activity of a specific splicing factor. Pharmaceutical compositions comprising the oligonucleotide and uses thereof are further disclosed.

Provided are therapeutic agents such as double-stranded nucleic acids, termed oligonucleotide decoys, pharmaceutical compositions comprising the same, and related methods of modulating nociceptive signaling, for instance, to prevent and/or treat pain.

The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

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.

The present disclosure provides compositions and methods for inhibiting herpesvirus replication in a cell infected with herpesvirus. The composition includes a double stranded DNA molecule including a sequence of a cis regulatory sequence (crs) of a herpesvirus, wherein the crs is flanked on the 5′ end by a first sequence of at least 2 base pairs and on the 3′ end by a second sequence of at least 2 base pairs.

The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.