In one aspect, the invention relates to a method of loading exosomes with oligonucleotide cargo, by incubating an oligonucleotide comprising one or more hydrophobic modifications with a population of exosomes for a period of time sufficient to allow loading of the exosomes with the oligonucleotide. Exosomes loaded with hydrophobically modified oligonucleotide cargo, and uses thereof, are also provided.

The invention provides an oligonucleotide comprising an inosine, and/or a nucleotide containing a base able to form a wobble base pair or a functional equivalent thereof, wherein the oligonucleotide, or a functional equivalent thereof, comprises a sequence which is complementary to at least part of a dystrophin pre-m RNA exon or at least part of a non-exon region of a dystrophin pre-m RNA said part being a contiguous stretch comprising at least 8 nucleotides. The invention further provides the use of said oligonucleotide for preventing or treating DMD or BMD.

A method of reducing the level of a transcription product in a cell comprising contacting with the cell a composition comprising a double-stranded nucleic acid complex comprising a first nucleic acid strand annealed to a second nucleic acid strand, wherein: (i) the first nucleic acid strand hybridizes to the transcription product and comprises (a) a region consisting of at least 4 consecutive nucleotides that are recognized by RNase H when the strand is hybridized to the transcription product, (b) one or more nucleotide analogs located on 5′ terminal side of the region, (c) one or more nucleotide analogs located on 3′ terminal side of the region and (d) a total number of nucleotides and nucleotide analogs ranging from 8 to 35 nucleotides and (ii) the second nucleic acid strand comprises (a) nucleotides and optionally nucleotide analogs and (b) at least 4 consecutive RNA nucleotides.

The present invention relates to a nucleic acid complex having a novel structure, which may introduce a bioactive nucleic acid into cells, a composition for treating or diagnosing disease comprising the same, and a method of regulating target gene expression using the same, and more particularly to a nucleic acid complex in which a bioactive nucleic acid, which comprises a material for facilitating endosomal escape, and a carrier peptide nucleic acid, are complementarily bound to each other, a composition for treating or diagnosing disease comprising the same, a composition for regulating target gene expression using the same, and a method of regulating target gene expression using the same.

A nucleic acid complex of Structural Formula (1) according to the present invention, which comprises a bioactive nucleic acid and a carrier peptide nucleic acid, may increase the stability of the bioactive nucleic acid, reduce loss of the bioactive nucleic acid, such as precipitation caused by self-aggregation, increase the intracellular delivery efficiency of the bioactive nucleic acid, and easily regulate target gene expression.

A skin-penetrating carrier containing a nucleic acid complex having a novel structure which introduces a bioactive nucleic acid into cells. Composition for diagnosing, preventing or treating disease and to a skin-penetrating carrier containing a nucleic acid complex in which a bioactive nucleic acid and a carrier peptide nucleic acid are complementarily bound to each other, and having skin permeability and skin retention ability. Skin-penetrating carrier containing nucleic acid complex having structure of Structural Formula (1) has both a skin penetration function of effectively delivering a large-molecular-weight drug and in vivo effectiveness. Carrier enables bioactive nucleic acids or various compounds to pass through the epidermis and dermis of the skin, thus enables external treatment by application to the skin surface.

The invention relates to a method wherein a molecule is used for inducing and/or promoting skipping of at least one of exon 43, exon 46, or exons 50-53 of the DMD pre-mRNA in a patient, the method comprising providing the patient with the molecule. The invention also relates to the molecule as such.

The present disclosure relates to antisense oligomers and related compositions and methods for increasing the expression of functional human type VII collagen and methods for treating dystrophic epidermolysis bullosa and related disorders and relates to inducing exclusion of exon 80 in human type VII collagen mRNA.

The present invention provides a natural type miRNA, which is a single-stranded nucleic acid containing X region and Y region, wherein the 3′-terminus of said X region and the 5′-terminus of said Y region are linked via a linker region of a non-nucleotide structure, the X region contains (a) a guide strand sequence or (b) a passenger strand sequence of a mature miRNA, when the X region contains (a), the Y region contains a passenger strand sequence of the mature miRNA, when the X region contains (b), the Y region contains a guide strand sequence of the mature miRNA, and the guide strand sequence and the passenger strand sequence form a double-stranded structure.

The present disclosure provides a method of modifying a globin gene in the genome of a hematopoietic stem/progenitor cell (HSPC), the method comprising: A) obtaining HSPCs from an individual having a globin gene comprising a sickle cell disease (SCD)-associated single nucleotide polymorphism (SNP) to generate an in vitro population of CD34+ HSPCs and B) contacting the in vitro population with a genome editing composition, as described in further detail below. Also provided is a method of treating sickle cell disease (SCD) in an individual including administering to an individual an in vitro mixed population derived from the method of modifying a globin gene, as well as kits for practicing the same.

Disclosed herein are heteroduplex nucleic acid molecules, heteroduplex nucleic acid conjugates, and pharmaceutical compositions for modulating a protein expression. Also described herein include methods of treating a disease or indication which utilize a heteroduplex nucleic acid molecule, a heteroduplex nucleic acid conjugate, or a pharmaceutical composition that comprises a heteroduplex nucleic acid molecule.