Abstract: Provided herein, in some embodiments, are materials and methods for treating hemophilia A in a subject ex vivo or in vivo. Also provided herein, in some embodiments, are materials and methods for knocking in a coding sequence encoding a synthetic FVIII having a B domain substitute into a genome.

Abstract: Disclosed herein are compositions and methods for cellular reprogramming. The compositions comprise one or more miRs and an activator of NF?B. Also provided are methods for enhancing or upregulating cardiomyocyte maturation in a cell or a subject and methods for inhibiting or downregulating cardiomyocyte maturation.

Abstract: RNAs, such as miRNA and siRNA, and their use in treating complement-mediated disorders, are described.

Abstract: The present disclosure provides compositions which shown preferential targeting or delivery of a nucleic acid composition to a particular organ. In some embodiments, the composition comprises a steroid or sterol, an ionizable cationic lipid, a phospholipid, a PEG lipid, and a permanently cationic lipid which may be used to deliver a nucleic acid.

Abstract: In the present invention it is shown that the inactivation of the Pyk2 gene does not alter hippocampal development but prevents hippocampal-dependent memory tasks and LTP. Inventors clearly provide evidence for multiple roles of Pyk2 in spine morphology and postsynaptic structure. Thus, the inventors used direct overexpression of PYK2 by AAV-mediated gene transfer into the brain of Huntington's and Alzheimer's mouse models and found that overexpression of PYK2 in these 2 models improves synaptic properties and spine density deficits which is also accompanied by a rescue of spatial memory. Accordingly it was demonstrated that PYK2 may restore cognitive functions in neurodegenerative diseases. Thus the present invention relates to methods and pharmaceutical compositions for the treatment of neurodegenerative disease.

Abstract: Compositions and methods for treating cancer are provided. In particular, the compositions comprise an anti-neoplastic agent and either an interferon type I agonist or an interferon type II agonist, or a combination of an interferon type I agonist and an interferon type II agonist.

Abstract: The present disclosure provides compositions and methods that inhibit the activity of microRNAs, for example miR-22.

Abstract: The present invention generally relates to specific immune-modulatory RNA species that have a small hairpin structure (shRNA), and that can bind to retinoic acid inducible gene I receptor (RIG-I). In particular, said RNA species comprise a nucleotide insertion to create a kink in the stem region. Also encompassed are compositions comprising such shRNA, for use as antiviral or anticancer medication, or as adjuvants in vaccine.

Abstract: Disclosed are compounds, compositions and methods for treating of diseases, syndromes, or disorders that are affected by the modulation of STING. Such compounds are represented by Formula (I) as follows: wherein R, R1B, R1C, R2B, R2C, B1, W, X, Y, Z are defined herein.

Abstract: The present invention relates to the use of a regulatory nucleic acid sequences that are able to regulate gene expression in eukaryotic cells and which are responsive to the unfolded protein response (UPR). There are disclosed regulatable introns and UPR-inducible promoters, which are able to regulate gene expression. There are also disclosed recombinant expression constructs comprising such regulatory nucleic acid sequences, whereby expression of the encoded expression product can be induced by invoking the unfolded protein response (UPR) in a eukaryotic cell containing the construct, methods of using such constructs and associated vectors, cells and suchlike.

Abstract: The present disclosure encompasses methods for generating cells or tissue from existing cells with one or more mutated variants of Yap. In specific embodiments, the disclosure regards treatment of existing cardiomyocytes with one or more mutated variants of Yap that causes them to divide and generate new cardiomyocytes. In specific cases, the mutated variant of Yap has serine-to-alanine substitutions at 1, 2, 3, 4, 5, 6, or more serines of Yap.

Abstract: The present disclosure provides messenger RNAs (mRNAs) having chemical and/or structural modifications, including RNA elements and/or modified nucleotides, which provide a desired translational regulatory activity to the mRNA.

Abstract: This disclosure relates to modified single and dual guide RNAs having improved in vitro and in vivo activity in gene editing methods.

Abstract: Provided is a novel technique for treating cancer using structurally-reinforced S-TuD. Provided are: a composition for the prevention or treatment of tumors, said composition comprising an miRNA inhibitory complex including RNA of analog thereof; and a method for preventing or treating tumors using said composition. The miRNA inhibitory complex preferably includes at least one double-stranded structure and an miRNA-binding sequence. Two strands of the miRNA binding sequence preferably bind individually to two strands on at least one end of the double-stranded structure. According to some of the aspects of the present invention, there is provided a delivery system for delivering such an miRNA inhibitory complex.

Abstract: The invention is directed to methods of treating TNBC in a patient by administering to the patient an agent that inhibits the expression or activity of cyclin-dependent kinase 19 (CDK19). In some embodiments, the agent may be a small molecule inhibitor, a polynucleotide (e.g., shRNA. siRNA), or a protein (e.g., an antibody). In some embodiments, the agent does not inhibit the activity or expression of CDK8.

Abstract: The present invention relates to an RNA suitable for treatment or prophylaxis of liver diseases. In particular, the present invention provides an RNA encoding at least one peptide or protein selected from the group consisting of an extracellular matrix protease, CCAAT/enhancer-binding protein alpha (CEBPA), TNF-related apoptosis-inducing ligand (TRAIL), Hepatocyte Growth Factor (HGF), hepatocyte nuclear factor 4 alpha (HNF4A), fibroblast growth factor 21 (FGF21), opioid growth factor receptor-like 1 (OGFRL1), Relaxin 1 (RLN1), Relaxin 2 (RLN2) and Relaxin 3 (RLN3), or a fragment or a variant of any of these peptides or proteins. The present invention concerns said RNA as well as compositions and kits comprising the RNA. Furthermore, the present invention relates to the RNA, compositions or kits as disclosed herein for use as a medicament, in particular for treatment or prophylaxis of a liver disease.

Abstract: Methods and compositions for treating cancer, e.g., colorectal cancer, using a miR-101-3p inhibitor.

Abstract: The present invention is related to a method for the preparation of a modified nucleic acid molecule comprising a nucleic acid moiety and a non-nucleic acid moiety by reacting a first reactant and a second reactant, wherein the first reactant comprises the non-nucleic acid moiety and a carboxyl group, and wherein the second reactant is an amino-modified nucleic acid molecule comprising the nucleic acid moiety and an amino modification comprising an amino group which is attached to the nucleic acid moiety, wherein the method comprises the following steps: a) activating the first reactant, preferably the carboxyl group of the first reactant, by a condensation reagent in a water miscible organic solvent, and b) reacting the activated first reactant, preferably the activated carboxyl group of the first reactant, of step a) and the second reactant, preferably the amino group of the amino modification of the amino-modified nucleic acid molecule which has been dissolved in water or a mixture of a water miscible orga

Abstract: The present invention generally relates to the field of molecular biology and RNA interference (RNAi). More specifically, the present invention relates to specific siRNA molecules, compositions and uses thereof, as well as methods of treating cancer and methods of inhibiting cancer cell proliferation, particularly methods of treating breast cancer. Yet more particularly, the methods of the present invention are methods for inhibiting growth of triple negative breast cancer (TNBC). In a preferred embodiment, the invention provides specific siRNA molecules, comprising a sequence selected from SEQ ID NO: 1 and SEQ ID NO: 2, and from any other sequence having a sequence identity greater than 90% between the siRNA and the portion of the target gene. Such siRNA molecules are suitable for the treatment of breast cancer, particularly, TNBC.

Abstract: The present invention encompasses genetically-modified immune cells (and populations thereof) expressing a microRNA-adapted shRNA (shRNAmiR) that reduces the expression of a target endogenous protein. Methods for reducing the expression of an endogenous protein in an immune cell are also provided wherein the method comprises introducing a shRNAmiR that targets the endogenous protein. Using shRNAmiRs for knocking down the expression of a target protein allows for stable knockdown of expression of endogenous proteins in immune cells.