The present disclosure relates to a compound including a nucleic acid sequence conjugated to an anti-microRNA or a microRNA-mimic or a compound including a modified anti-microRNA sequence, compositions of such a compound, and method of treatment of a disease, and method of suppressing microRNA activity by the disclosed compound or composition.

A system for editing of a target sequence at a locus of a host cell is disclosed. The system has a nucleic acid molecule comprising a nucleic acid segment comprising a targeting RNA sequence and an RNA segment that binds a protein. The system also has a nucleic acid molecule comprising a nucleic acid segment encoding a polypeptide with endonuclease activity fused to a protein that binds the RNA segment. The system also comprises a double stranded DNA molecule comprising DNA comprising at least one nucleotide sequence that is capable of binding to the target sequence at the locus.

The present technology relates, in part, to long double-stranded RNA (dsRNA) (e.g., 30 or more base pairs) that inhibits gene expression.

A DNA methylation editing kit comprises: (1) a fusion protein of inactivated CRISPR-associated endonuclease Cas9 (dCas9) having no nuclease activity and a tag peptide array in which plural tag peptides are linked by linkers, or an RNA or DNA coding therefor; (2) a fusion protein(s) of a tag peptide-binding portion and a methylase or demethylase, or an RNA(s) or DNA(s) coding therefor; and (3) a guide RNA(s) (gRNA(s)) comprising a sequence complementary to a DNA sequence within 1 kb of a desired site of methylation or demethylation, or a DNA(s) expressing the gRNA(s).

A hyperbranched polymer includes a hyperbranched, hydrophobic molecular core, respective low molecular weight polyethyleneimine chains attached to at least three branches of the hyperbranched, hydrophobic molecular core, and respective polyethylene glycol chains attached to at least two other branches of the hyperbranched, hydrophobic molecular core. Examples of the hyperbranched polymer may be used to form hyperbranched polyplexes, and may be included in DNA or RNA delivery systems.

Recent advancements in LNA oligonucleotides include the use of amine linkers to link an LNA antisense oligonucleotide to a conjugate group. For example please see WO2014/I18267. The present invention originates from the identification of a problem when de-protecting LNA oligonucleotides which comprise an aliphatic amine group and DMF protected LNA G nucleoside, which results in the production of a +28 Da impurity. This problem is solved by using acyl protection groups on the exocyclic nitrogen of the LNA-G residue, rather than the standard DMF protection group.

The present invention provides method of increasing the efficacy and potency of antisense compounds. In certain embodiments, the invention provides methods for improved cellular uptake.

Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 53 skipping are described.

Disclosed herein are methods, compositions, polynucleic acid polymers, assays, and kits for inducing processing of a partially processed mRNA transcript to remove a retained intron to produce a fully processed mRNA transcript that encodes a full-length functional form of a protein. Also described herein are methods and compositions for treating a disease or condition characterized by impaired production of a full-length functional form of a protein or for treating a disease or condition characterized by a defective splicing in a subject.

Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine.