The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting an APOE gene, as well as methods of inhibiting expression of an APOE gene and methods of treating subjects having an APOE-associated neurodegenerative disease or disorder, e.g., Alzheimer's disease and Parkinson's disease, using such dsRNAi agents and compositions.

A multi-targeted siRNA for treating cancers is disclosed. Specifically, an siRNA composition is provided, comprising: a first siRNA molecule that reduces the expression of the first target gene; optionally, a coding sequence targeting a peptide element; and optionally, a second siRNA molecule that reduces the expression of the second target gene, wherein the first target gene is selected from the group consisting of EGFR, KRAS, or a combination thereof, and the siRNA composition reduces the expression of two or more genes. The siRNA or vector provided can be directly injected into the body to treat cancers.

A multi-targeted siRNA for treating cancers is disclosed. Specifically, an siRNA composition is provided, comprising: a first siRNA molecule that reduces the expression of the first target gene; optionally, a coding sequence targeting a peptide element; and optionally, a second siRNA molecule that reduces the expression of the second target gene, wherein the first target gene is selected from the group consisting of EGFR, KRAS, or a combination thereof, and the siRNA composition reduces the expression of two or more genes. The siRNA or vector provided can be directly injected into the body to treat cancers.

Provided herein are aptamers that target cytotoxic T-lymphocyte and methods of use thereof.

An oligonucleotide having a nucleotide residue or a nucleoside residue represented by formula (I) {wherein X.sup.1 is an oxygen atom or the like, R.sup.1 is formula (IIA) (wherein R.sup.5A is halogen or the like, and R.sup.6A is a hydrogen atom or the like), formula (IVA) (wherein Y.sup.3A is a nitrogen atom or the like, and Y.sup.4A is CH or the like), or the like, R.sup.2 is a hydrogen atom, hydroxy, halogen, or optionally substituted lower alkoxy, and R.sup.3 is a hydrogen atom or the like, or formula (VI) (wherein n2 is 1, 2 or 3)} at the 5′ end thereof, wherein the nucleotide residue or the nucleoside residue binds to an adjacent nucleotide residue through the oxygen atom at position 3, is provided.

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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.

Disclosed are DsiRNA inhibitors for the genes encoding SAV1, NF2 and MOB1, which cause proliferation of cardiomyocytes on administration to a mammal. The DsiRNA inhibitors can also be administered with a mutant SRF(153-A3) or an mRNA encoding it, and/or Yap5SA (a Yap mutant) or an encoding mRNA, which enhance the proliferative effect on cardiomyocytes. Mutant SRF(153-A3) with Yap5SA alone also induce myocyte replication.

The invention provides methods and compositions for enhancing the efficacy of cancer therapies through modulation of BAL1 and/or BBAP. Also provided are methods for predicting the efficacy of cancer therapies or treating cancer in a subject through modulation of BAL1 and/or BBAP. Further provided are methods for identifying compounds that are capable of modulating BAL1-BBAP complexes.

The present disclosure is broadly concerned with the field of cancer immunotherapy. For example, the present invention generally relates to an immune cell comprising a genetically engineered antigen receptor that specifically binds to a target antigen and a genetic disruption agent that reduces or is capable of reducing the expression in the immune cell of a gene that weakens the function of the immune cell.

The present invention is based on the finding that CD11b signaling inhibits immune suppression, modulates neovascularization and promotes anti-tumor immune responses in models of murine and human cancer. As such, provided herein are methods of treating cancer using an antibody, protein or small molecule that modulates CD11b activity or expression. Also provided are methods of identifying cancer that is amenable to such treatment and/or increasing susceptibility of cancer cells to treatment with a chemotherapeutic agent.

In various embodiments a cancer treatment method is provided based on inhibition of proline catabolism. When combined with p53 restoration therapy and/or inhibition of glutaminase, the inhibition of proline catabolism results in a “synthetic lethal” and synergistic anticancer response. Novel suicide inhibitors that induce the degradation of proline dehydrogenase (PRODH) are also provided. Also provided is a method of assaying PRODH to identify responders/non-responders to inhibition of proline catabolism and/or glutaminase.