Compositions and methods for introducing double-stranded breaks within the SERPINA1 gene are provided. Compositions and methods for reducing and eliminating mutant forms of α1-antitrypsin (AAT), such as seen in subjects having α1-antitrypsin deficiency (AATD), are provided.

A gene-editing system includes an engineered photocleavable guide RNA to endow Cas9 nuclease and base editing activities with a built-in mechanism for fast, light-mediated deactivation. In methods of use, the system retains high editing efficiency, natively improves specificity, offers precise spatial and temporal control, improves base editing purity through early deactivation.

This application relates to therapeutic siRNA agents and methods of making and using the agents.

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.

One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. Other aspects of the invention relate to pharmaceutical compositions comprising these dsRNA molecules suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA molecules, e.g., for the treatment of various disease conditions.

The invention provides an artificial sgRNA and a CRISPR/Cas9 system by combining the artificial sgRNA and Cas9. Activity of the sgRNA can be retained even when a nucleotide linker region for forming a single strand by linking the 3′-terminal of crRNA and the 5′-terminal of tracrRNA in sgRNA is substituted with an amino acid derivative linker, when the linker region existing between stem-loop 1 and stem-loop 2 of tracrRNA and/or the loop portion of stem-loop 2 are/is substituted with an amino acid derivative linker, or when an amino acid derivative linker is added/inserted into the vicinity of the 5′-terminal and/or the 3′-terminal of sgRNA. Stability in vivo can be improved by introducing one or more amino acid derivative linkers into the sgRNA.

The present disclosure relates to methods of treating heat shock factor 1 (HSF1)-related diseases such as cancer and viral diseases, using a therapeutically effective amount of a RNAi agent to HSF.

The present disclosure relates to double-stranded oligonucleotides, including double-stranded oligonucleotides such as siRNAs, comprising a sense strand oligonucleotide and an antisense strand oligonucleotide, and wherein the antisense strand oligonucleotide comprises one or more nucleotide analogs of formula (I-A) which are neither the 5′-overhang nucleotide nor the 3′-overhang nucleotide of the said antisense strand oligonucleotide, and wherein a nucleotide analog of formula (I-A) is as described in the disclosure. Oligonucleotides containing these analogs have superior biological activity, for example, increased in vitro stability and improved in vivo potency especially improved off-target profiles. The improved oligonucleotides are useful for silencing (e.g., reducing or eradicating) the expression of a target gene.

This disclosure relates to modified guide RNAs having improved in vitro and in vivo activity in gene editing methods.

Compositions for providing stability to RNA may include a primary surfactant, and a metal-ion sequestrant. The primary surfactant may be a nonionic surfactant. The composition may be in a soluble liquid concentrate form and may be sufficient to provide shelf stability to RNA for one year at room temperature. Compositions for delivering RNA to a pest via exogenous, foliar application of the composition to a plant may comprise RNA; a primary surfactant; and a metal-ion sequestrant.