The present invention is related to a ribonucleic acid comprising a double stranded structure whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.

The present invention relates to the combination of a Dbait molecule with a KRAS inhibitor for treating cancer.

The present invention relates to a method for treating ocular disease in a subject in need thereof comprising a step of administering to said subject a therapeutically amount of an inhibitor of SOX21 gene expression and/or activity. By studying a mouse model of congenital microcoria, the inventors demonstrate that this ultra-rare and purely ocular disease is due to unanticipated complex mechanisms linked with 3D regulation of gene expression. They propose that the disease is due to the illegitimate expression of a transcription factor, SOX21, induced by the adoption of a DCT enhancer(s). They show that SOX21 binds to a regulatory region of the Tgfβ2 gene and the inventors demonstrate overexpression of this trophic factor in the iris and accumulation of its product in the aqueous humor of the mouse carrying the minimal MCOR deletion which recapitulates the observed accumulation in patients with POAG and one of our patient with MCOR.

Disclosed herein, inter alia, are compositions and methods of modulating macrophage activity. Provided is a method of treating a disease (e.g., a macrophage-associated disease, autoimmune disease, inflammatory disease, or a cancer of an organ in the intraperitoneal cavity), the method including intraperitoneally administering to a subject in need thereof a therapeutically effective amount of a nanoparticle composition or pharmaceutical composition. Provided is a silica nanoparticle non-covalently bound to a plurality of nucleic acids, wherein the silica nanoparticle has a net positive charge in the absence of the plurality of nucleic acids. Provided is a pharmaceutical composition including a nanoparticle composition as described herein, and a pharmaceutically acceptable excipient.

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.

The present disclosure belongs to the technical field of biomedicine, and provides an engineered circular RNA circmiR-29b and use thereof in preparation of a medicine for treating muscle atrophy. The present disclosure provides a circular RNA circmiR-29b including an effective sequence and a random sequence, wherein 6-13 repetitions of the effective sequence are connected in series, the random sequence is inserted between the effective sequences, and the nucleotide sequence of the effective sequence is shown in SEQ ID NO: 1. The present disclosure delivers circmiR-29b to skeletal muscle by AAV8, enabling stable expression of circmiR-29b in the skeletal muscle, thereby effectively inhibiting various types of muscle atrophy. Therefore, the present disclosure also provides a gene therapy based on the AAV8 virus vector delivering the engineered circular RNA circmiR-29b to achieve the objective of treating muscle atrophy.

Polynucleotide constructs are disclosed, that are potent activators of a STING-independent DNA sensing pathway (SIDSP), in which the DNA damage response protein DNA-PK is the sensor of the SIDSP, along with tire heat shock protein HSPA8 as a unique SIDSP target. The polynucleotide constructs of the disclosure are also potent activators of the cGAS-STING DNA sensing pathway. These pathways arm key components of the innate immune response that is important for antiviral immunity, contributes to specific autoimmune diseases, and mediate important aspects of antitumor immunity.

Among the various aspects of the present disclosure is the provision of a method of treating a neurodegenerative disease in a subject in need thereof comprising administering a therapeutically effective amount of a TAR DNA-binding protein (TDP-43) modulating agent comprising an RNA oligonucleotide.

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.

Provided herein are methods and compositions for long term treatment of spinal pain. In particular, use of double-stranded oligonucleotide decoys capable of binding to the DNA binding sites of two transcription factors are provided for treatment of spinal pain for over seven days, where the decoys are administered without a drug delivery system.