Chemically modified Neisseria meningitidis (Nme) crRNAs, tracrRNAs, and sgRNAs are provided. Methods of using the Nme crRNAs, tracrRNAs, and sgRNAs for genome editing with a Nme CRISPR nuclease and kits for performing the same are also provided.

The present invention is directed to compounds, compositions, and methods useful for modulating PD1, PDL1, IDO1, LAG3, TIM3, CTLA4, IDO2, CEACAM1, OX40, and/or OX40L mRNA or protein expression using gene silencing compounds comprising two or more single stranded antisense oligonucleotides that are linked through their 5′-ends to allow the presence of two or more accessible 3′-ends.

A double-stranded nucleic acid complex that can have an excellent activity is provided. In one embodiment, the present invention relates to a double-stranded nucleic acid complex having a first nucleic acid strand and a second nucleic acid strand. The first nucleic acid strand is capable of hybridizing to at least part of a target gene or a transcription thereof, has an antisense effect on the target gene or transcription product thereof, and has at least two morpholino nucleic acids The second nucleic acid strand has a base sequence complementary to the first nucleic acid strand. The first nucleic acid strand is annealed to the second nucleic acid strand.

The present invention relates to methods for treating and preventing ophthalmological disease and disorders, comprising administering Antagonist A or another pharmaceutically acceptable salt thereof, optionally in combination with another treatment, to a subject in need thereof. The present invention also relates to methods for treating and preventing ophthalmological disease and disorders, comprising administering an anti-C5 agent (e.g., ARC1905), optionally in combination with another treatment, to a subject in need thereof.

The methods and compositions of the disclosure provide for novel therapeutic compounds to treat obesity and aspects related thereto. Embodiments of the disclosure relate to oligonucleotide therapeutic (ONT) agents targeting miR-22 miRNA for the treatment of human obesity and related cardiometabolic disorders. Accordingly, aspects of the disclosure relate to modified nucleic acids, including locked nucleic acids, ethylene-bridged nucleotides, peptide nucleic acids, phosphorodiamidate morpholino oligonucleotides, and or a 5′(E)-vinyl-phosphonate modification.

Oligonucleotides that target hepatitis B virus (HBV) viral sequences, such as rcDNA, cccDNA, and HBV transcripts, are described herein. In addition, compositions and kits comprising such oligonucleotides are further described. Further disclosed herein are uses of such oligonucleotides and compositions to reduce rcDNA to cccDNA conversion, reduce cccDNA levels, and/or treat an HBV infection.

Functionally-modified oligonucleotide analogs comprising modified intersubunit linkages and/or modified 3′ and/or 5′-end groups are provided. The disclosed compounds are useful for the treatment of diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.

Methods of using B2 or Alu nucleic acids, or antisense oligonucleotides that modulate the EZH2/B2 or EZH2/Alu interaction and have the capacity to alter cleavage of B2 and Alu RNA, for increasing or decreasing cell and organismal viability.

An isolated oligonucleotide comprising ribonucleotides is disclosed. The oligonucleotide comprises a nucleic acid sequence which encodes at least one copy of a splicing-factor binding site. The oligonucleotide is no more than 150 bases and may be devoid of a sequence that allows hybridization thereof to cellular RNA under physiological conditions. The oligonucleotide inhibits overall cellular splicing activity of a specific splicing factor. Pharmaceutical compositions comprising the oligonucleotide and uses thereof are further disclosed.

Presented is a method for treating inflammation and autoimmune diseases through the use of a phosphatase rheumatoid arthritis (PT-PRA) antagonist.