A manufacturing method for a single-stranded RNA includes a step of causing an RNA ligase to act on a first single-stranded RNA having a phosphate group at the 5 end and a second single-stranded RNA having a hydroxyl group at the 3 end to link the first single-stranded RNA and the second single-stranded RNA. The first single-stranded RNA is a single-stranded RNA consisting of an X1 region and a Z region in order from the 5 end; the second single-stranded RNA is a single strand consisting of an X2 region, a Y2 region, a Ly linker region, and a Y1 region in order from the 5 end; the X1 region and the X2 region have nucleotide sequences which are complementary to each other, have a length of at least two nucleotides, and have the same number of nucleotides; and the Y1 region and the Y2 region have nucleotide sequences which are complementary to each other, have a length of at least two nucleotides, and have the same number of nucleotides.

A method produces a hairpin single-stranded RNA molecule capable of inhibiting expression of a target gene, the method including: (i) an annealing step of annealing a first single-stranded oligoRNA molecule and a second single-stranded oligoRNA molecule; and (ii) a ligation step of ligating 3 end of the first single-stranded oligoRNA molecule and 5 end of the second single-stranded oligoRNA molecule by an Rnl2 family ligase, wherein a sequence produced by ligating the first single-stranded oligoRNA molecule and the second single-stranded oligoRNA molecule includes a gene expression-inhibiting sequence for the target gene.

The present disclosure provides oligomeric compound comprising a modified oligonucleotide having a central region comprising one or more modifications. In certain embodiments, the present disclosure provides oligomeric compounds having an improved therapeutic index or an increased maximum tolerated dose.

The invention relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting the SCAP gene, as well as methods of inhibiting expression of a SCAP gene and methods of treating subjects having a SCAP-associated disorder, such as nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH), using such dsRNAi agents and compositions.

Methods and constructs for RNA-guided targeting of transcriptional activators to specific genomic loci.

Provided herein are, inter alia, methods of treating red blood cell disorders and cancer using anti-miR126 compounds. The methods include administering phosphorothioated CpG oligodeoxynucleotides conjugated to an anti-miR126 nucleic acid sequence to treat red blood cell disorders. Other methods provided herein include administering phosphorothioated CpG oligodeoxynucleotides conjugated to an anti-miR126 nucleic acid sequence and a tyrosine kinase inhibitor to treat cancer.

The invention relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting the SCAP gene, as well as methods of inhibiting expression of a SCAP gene and methods of treating subjects having a SCAP-associated disorder, such as nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH), using such dsRNAi agents and compositions.

Methods and constructs for RNA-guided targeting of transcriptional activators to specific genomic loci.

In one aspect, a chemically-modified siRNA for reversible photo-controlled gene silencing is provided. In one embodiment, one or more nucleotides the sense strand of the siRNA are replaced with a spacer comprising an azobenzene or derivative thereof. The azobenzene or derivative thereof undergoes isomerization between the trans-configuration and the cis-configuration in the presence of light from a light source and the siRNA optionally has higher RNA silencing activity when the azobenzene or derivative thereof is in the trans-configuration compared to the cis-configuration. In other aspects, the chemically-modified siRNAs may, for example, be useful as both therapeutics and research tools.

Methods and constructs for the multiplex expression of highly active CRISPR guide RNAs (gRNAs) from RNA Polymerase II and III promoters, optionally in mammalian cells.