Abstract: The invention relates to nucleic acid molecules for pseudouridylation of a target uridine in a target RNA in a mammalian cell, wherein the nucleic acid molecule comprises a guide region capable of forming a partially double stranded nucleic acid complex with the target RNA comprising the target uridine, wherein the partially double stranded nucleic acid complex is capable of engaging a mammalian pseudouridylation enzyme, wherein the guide region assists in positioning the target uridine in the partially double stranded nucleic acid complex for it to be converted to a pseudouridine by the mammalian pseudouridylation enzyme.

Abstract: The present invention is directed to antisense oligomeric compounds that may be used in the treatment Pompe disease as well as method for modulating the splicing of the GAA gene and method to treat Pompe disease. Also pharmaceutical compositions comprising the antisense oligomeric compounds are part of the invention.

Abstract: The present disclosure provides compositions comprising an antisense oligonucleotide and one or more excipients that modulates viscosity, turbidity or both viscosity and turbidity. In certain embodiments, compositions comprising an antisense oligonucleotide and one or more excipients having low viscosity are provided. In certain embodiments, compositions comprising an antisense oligonucleotide and one or more excipients having low turbidity are provided. In certain embodiments, pharmaceutical compositions comprising an antisense oligonucleotide and one or more excipients having low viscosity and turbidity are provided.

Abstract: The invention relates to double stranded ribonucleic acid (dsRNA) compositions targeting a glucokinase (GCK) gene, as well as methods of inhibiting expression of a glucokinase (GCK) gene, and methods of treating subjects having a glycogen storage disease (GSD), e.g., type Ia GSD.

Abstract: Described herein are cell-selective mRNA constructs that can contain a RNA of interest and one or more miRNA targets. The cell-selective mRNA constructs described herein can be used to express an RNA of interest to a cell in a cell-selective manner.

Abstract: An object of the invention is to provide a low toxicity antisense nucleic acid medicine that can modulate expression of a target transcriptional product in the central nervous system and other sites of a subject. Provided is a low toxicity composition for modulating expression of a target transcriptional product in a site such as the central nervous system of a subject, having a nucleic acid complex formed by annealing together a first nucleic acid strand having an antisense oligonucleotide region with respect to the target transcriptional product, and a second nucleic acid strand having a complementary region that is complementary to at least part of the first nucleic acid strand.

Abstract: The disclosure relates, in some aspects, to compositions and methods for treating corneal disease (e.g., corneal neovascularization. In some embodiments, the disclosure relates to rAAV-mediated delivery of an cornea-associated transgene to a subject. In some embodiments, the rAAV transduces the corneal tissue of a subject.

Abstract: This invention relates generally to pharmaceutical compositions and preparations of circular polyribonucleotides and uses thereof.

Abstract: Provided herein are compositions and methods for reducing expression of C9orf72 transcripts in cells containing expanded intronic GGGGCC regions, including those in subjects having or at risk of developing amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

Abstract: The present disclosure provides methods of treating or preventing fatty liver disease and/or lowering cholesterol and LDL cholesterol levels in a subject. The present disclosure further provides methods of lowering expression of Pleckstrin and Sec7 Domain Containing 3 (PSD3) in a subject.

Abstract: The invention relates to nucleic acid products that interfere with or inhibit PROS1 gene expression. It further relates to therapeutic uses of PROS1 inhibition for the treatment of bleeding disorders.

Abstract: Provided herein are methods and compositions for treating cancer, including cancer that is not responsive to immunotherapy. In one aspect, the methods of treatment comprise administering to the subject a therapeutically effective amount of a ?-catenin inhibitor, a therapeutically effective amount of an IDO inhibitor, and a therapeutically effective amount of an immunotherapeutic agent. Another aspect is directed to pharmaceutical compositions comprising a ?-catenin inhibitor for use in treating cancer, wherein the composition is administered in combination with an IDO inhibitor and an immunotherapeutic agent. Yet another aspect is directed to a method of potentiating the therapeutic effect of immunotherapy against a cancer using a ?-catenin inhibitor, such as a ?-catenin nucleic acid inhibitor molecule, in combination with an IDO inhibitor.

Abstract: The present invention relates, in part, to methods for detecting nuclease activity, such as the activity of Cas nucleases. Also described herein are compositions for conducting assays, as well as methods for conducting assays in the presence of test compounds.

Abstract: The present disclosure relates to compositions and methods for treating cancers using antisense (AS) nucleic acids directed against Insulin-like Growth Factor 1 Receptor (IGF-1R). The AS may be administered to the patients systemically, or may be used to produce an autologous cancer cell vaccine. In embodiments, the AS are provided in an implantable irradiated biodiffusion chamber comprising tumor cells and an effective amount of the AS. The chambers are irradiated and implanted in the abdomen of subjects and stimulate an immune response that attacks tumors distally. The compositions and methods disclosed herein may be used to treat many different kinds of cancer, for example glioblastoma.

Abstract: This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.

Abstract: Disclosed herein are engineered oligonucleotides for selective inhibition of polypeptide expression and activity. Also disclosed herein are methods of selectively inhibiting polypeptide expression and activity contacting an engineered oligonucleotide with a polynucleotide encoding the polypeptide.

Abstract: Described are compounds and methods useful for the treatment and investigation of Friedreich's Ataxia.

Abstract: The present disclosure provides expression vectors comprising at least two nucleic acid sequences, namely a nucleic acid sequence encoding an anti-HPRT RNAi, and a nucleic acid sequence encoding a gamma globin gene. In some embodiments, the viral vector is a self-inactivating lentiviral vector. In some embodiments, the gamma-globin gene is used to genetically correct sickle cell disease or ?-thalassemia or to reduce symptoms thereof.

Abstract: Cas-protein-ready tau bio sensor cells, CRISPR/Cas synergistic activation mediator (SAM)-ready tau biosensor cells, and methods of making and using such cells to screen for genetic vulnerability associated with tau aggregation are provided.

Abstract: The invention relates to the field of RNA stabilisation, and more particularly to the use of deuterium oxide (D2O) during storage and/or synthesis of RNA molecules. Described herein are deuterium-stabilised ribonucleic acid (RNA) molecules that display an increased resistance to thermal and enzymatic hydrolysis. Also described are aqueous compositions comprising stabilized RNA molecules and methods for making same. The invention is particularly useful for in the manufacture of RNA-based therapeutics, such as mRNA vaccines, to render them less sensitive to temperature fluctuations.