The current invention includes systems, methods and compositions for the generation of sRNA molecules using select RNase III mutants. In one preferred embodiment, invention includes systems, methods and compositions for the generation of sRNA molecules using RNase III mutants to control a host pathogen through the production and diffusion of sRNA molecules that may initiate an RNAi pathway response directed to a host pathogen. Additional embodiments of the current invention include systems, methods and compositions for the DICER-independent generation of sRNA molecules using select RNase III mutants.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of gene expression and/or activity, and/or modulate a gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against target gene expression.

The present invention relates to a pharmaceutical composition for preventing or treating dementia, containing a nucleic acid complex in which a carrier peptide nucleic acid and a bioactive peptide nucleic acid having a sequence for binding to a NLRP3 gene are complementarily bound. The nucleic acid complex according to the present invention has a blood-brain barrier penetration ability and can effectively inhibit expression and phosphorylation of the protein of the NLRP3 gene and tau, which a lower-level gene, and thus is useful in the prevention or treatment of dementia.

The present invention provides methods of protecting ribonucleic acid (RNA) from degradation under certain conditions by contacting the RNA with compounds that contain at least one boron atom. The present invention also provides compositions comprising such compounds and RNA.

The current invention includes systems, methods and compositions for the generation of sRNA molecules using select RNase III mutants. In one preferred embodiment, invention includes systems, methods and compositions for the generation of sRNA molecules using RNase III mutants to control a host pathogen through the production and diffusion of sRNA molecules that may initiate an RNAi pathway response directed to a host pathogen. Additional embodiments of the current invention include systems, methods and compositions for the DICER-independent generation of sRNA molecules using select RNase III mutants.

The disclosure includes antisense oligonucleotides (ASOs), including gapmer ASOs, and methods of making and using the same.

The invention provides, among other things, methods of stabilizing mRNA and nuclease resistant mRNA prepared in accordance with such methods. hi certain embodiments, the nuclease resistant mRNA encodes a functional protein, such as enzyme, and is characterized by its resistance to nuclease digestion, increased half-life and/or its ability to produce increased amounts of the functional protein (e.g., enzyme) encoded thereby.

One aspect of the present invention relates to double-stranded RNAi (dsRNA) duplex agent capable of inhibiting the expression of a target gene. The dsRNA duplex comprises one or more motifs of three identical modifications on three consecutive nucleotides in one or both strand, particularly at or near the cleavage site of the strand. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.

Compositions and methods for down modulating target gene expression which RNA interference, as well as methods for administering said compositions are disclosed. The method comprises administering a first oligonucleotide strand to a cell, incubating the cells for a time period suitable for uptake of the first oligo nucleotide strand prior to administration of a second oligonucleotide strand, wherein the first strand and the second strand form an intracellular duplex which is effective to catalyze degradation of gene target mRNA or inhibit translation of said mRNA.

The present disclosure provides DNA-guided CRISPR systems; polynucleotides comprising DNA, RNA and mixtures thereof for use with CRISPR systems; and methods of use involving such polynucleotides and DNA-guided CRISPR systems.