The present disclosure relates generally to modulation of genomic complexes via modulation of non-genomic components such as, non-coding RNAs.

Provided is a single-stranded oligonucleotide that is capable of controlling a target gene with high efficiency and can be easily produced. The single-stranded oligonucleotide is represented by the formula X-L-Y wherein X and Y hybridize by a first nucleotide sequence portion and a second nucleotide sequence portion. X is composed of 7 to 100 nucleotides, contains at least one modified nucleotide, and has a first nucleotide sequence that is capable of hybridizing with a second oligonucleotide and contains at least four contiguous nucleotides recognized by RNase H. Y is composed of 4 to 100 nucleotides, and has a second nucleotide sequence that is capable of hybridizing with a second oligonucleotide and contains at least one ribonucleotide. At least one of nucleotide sequence X and nucleotide sequence Y has an antisense sequence capable of hybridizing with a target RNA. L is a group derived from a third oligonucleotide that is degraded under physiological conditions.

A mutant SaCas9 protein such as a protein having an amino acid sequence resulting from mutations of glutamic acid at the 782-position to lysine (E782K), leucine at the 800-position to arginine (L800R), asparagine at the 968-position to arginine (N968R), asparagine at the 985-position to alanine (N985A), arginine at the 991-position to alanine (R991A), alanine at the 1021-position to serine (A1021S), threonine at the 927-position to lysine (T927K), lysine at the 929-position to asparagine (K929N), and isoleucine at the 1017-position to phenylalanine (I1017F) in SEQ ID NO: 2 has relaxed restriction on target sequence while maintaining binding ability to guide RNA, and is useful as a tool for gene editing.

The present invention relates to RNA, particularly an immunostimulatory RNA (isRNA), a coding RNA or a combination thereof, for use in the treatment or prophylaxis of a disease, in particular a tumor and/or cancer disease. The present invention also provides pharmaceutical compositions, and a kit comprising the RNA(s). Further, the invention also comprises medical uses of the RNA(s) and compositions comprising the RNA(s).

The present invention relates to pharmaceutical compositions for preventing or treating pulmonary metastasis of cancer. More specifically, the present invention relates to compositions that enhance anti-cancer immunity of the lung rather than induce death of advanced cancer, thus being effective in inhibiting, preventing or treating pulmonary metastasis of cancer.

Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods for treating Facioscapulohumeral muscular dystrophy.

The present invention relates to the treatment of muscular diseases.

Complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide are provided. Compositions and methods for delivery of complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide to mammals for both research and therapeutic use are provided. Methods of treating or reducing one or more symptoms of type 2 diabetes, prediabetes and/or gestational diabetes are provided.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits activity of a pro-atrophy gene. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

The present invention relates to an asymmetric siRNA that may inhibit expression of programmed cell death protein 1 (PD-1), and a use thereof, and more specifically, to: an asymmetric siRNA including an antisense strand including a sequence complementary to mRNA encoding PD-1, and a sense strand forming complementary bonds with the antisense strand; a pharmaceutical composition for preventing or treating cancer, including the asymmetric siRNA; an immune cell in which expression of PD-1 is inhibited, obtained by treatment with the siRNA; and an immune cell therapeutic agent for treating cancer, including the immune cell.