A method for determining nitric oxide concentration in biological samples. The method includes for determining nitric oxide concentration in a sample including: (i) providing a nucleic acid complex comprising a first single-stranded nucleic acid molecule comprising a fluorophore crosslinked to the first strand, the fluorophore comprising diaminorhodamine-4-methylamine (DAR-4M) conjugated, to dibenzocyclooctyne-polyethylene glycol (DBCO-PEGn) linker, wherein n equals 4-12 and a second single-stranded nucleic acid molecule that is partially or fully complementary to the first single-stranded molecule, wherein the nucleic acid complex further comprises a first label and a targeting moiety conjugated to the first single-stranded nucleic acid molecule or the second single-stranded nucleic acid molecule, the first label is capable of producing a signal, wherein the intensity of the signal is dependent at least on concentration of the nucleic acid complex in the sample; (ii) contacting the sample with the nucleic acid complex; (iii) measuring the intensity of the signal: and (iii) determining the nitric oxide concentration from the measured signal. Compositions for determining nitric oxide concentrations in biological samples are also included.

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of APP RNA in a cell or animal, and in certain instances reducing the amount of APP protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease or disorder. Such symptoms and hallmarks include cognitive impairment, including a decline in memory and language skills, behavioral and psychological symptoms such as apathy and lack of motivation, gait disturbances and seizures, progressive dementia, and abnormal amyloid deposits.

The present invention aims at establishing a novel therapy for facioscapulohumeral muscular dystrophy.

An oligonucleotide or a pharmaceutically acceptable salt thereof, wherein the oligonucleotide comprises an oligonucleotide of 15-30 bases consisting of a nucleotide sequence complementary to the region of nucleotide Nos. 502-556 or 578-612 of DUX4-fl mRNA consisting of the nucleotide sequence as shown in SEQ ID NO: 1; the 5′ and/or 3′ end of the oligonucleotide may be chemically modified; and the oligonucleotide is capable of switching the splice form of the DUX4 gene from DUX4-fl to DUX4-s. A pharmaceutical drug comprising the above oligonucleotide or a pharmaceutically acceptable salt thereof (e.g. therapeutic for facioscapulohumeral muscular dystrophy).

Methods of treating and preventing diseases associated with fibrosis are disclosed, as well as agents for use in such methods. The methods comprise inhibiting at least one of ITFG1, MFAP4, GRHPR, ABCC4, PAK3, TRNP1, APLN, KIF20A, and† or LTB. In one embodiment, the disease is a liver disease or condition. Also disclosed are methods of promoting regeneration of cells, such as hepatocytes.

The present invention relates to ocular administration of sd-rxRNA and rxRNAori molecules.

Oligonucleotides and compositions including the same are disclosed for inhibiting or reducing patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene expression. Methods of making and using the oligonucleotides also are disclosed, particularly uses relating to treating diseases, disorders and/or conditions associated with PNPLA3 expression.

Products, compositions, and their uses are provided. In particular, nucleic acid products that modulate, in particular interfere with or inhibit, Factor XI (FXI) gene expression are provided. The products can be oligomeric compounds that comprise at least a first region of linked nucleosides having at least a first nucleobase sequence that is at least partially complementary to at least a portion of RNA transcribed from an FXI gene, wherein said first nucleobase sequence is selected from the following sequences, or a portion thereof: SEQ ID NOs 1 to 250.

The disclosure is generally related to spherical nucleic acids (SNAs), structures comprising a nanoparticle core surrounded by a shell of oligonucleotides. In some aspects the disclosure provides a spherical nucleic acid (SNA) comprising: (a) a nanoparticle core; and (b) a shell of oligonucleotides attached to the nanoparticle core, wherein one or more oligonucleotides in the shell of oligonucleotides is attached to the nanoparticle core through a hydrophobic anchor comprising one or more dodecane (C12) subunits. Methods of making and using the SNAs are also provided herein.

Disclosed herein are novel lipids and liposomal compositions prepared using such compounds and related methods of neutralizing or otherwise modifying such liposomal compositions. The lipids described herein are useful for example, as liposomal vehicles to facilitate the delivery of encapsulated polynucleotides to target cells and the subsequent transfection of such target cells. In certain embodiments, one or more of the compounds that comprise the liposomal delivery vehicle may be neutralized or further modified such that the properties of the liposomal delivery vehicle are modified.

The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a SOD1 gene, as well as methods of inhibiting expression of a SOD1 gene and methods of treating subjects having a SOD1-associated neurodegenerative disease or disorder, e.g., Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Down's syndrome (DS), using such dsRNAi agents and compositions.