The present invention is related to a ribonucleic acid comprising a double stranded structure whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.

Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods for treating muscle atrophy or myotonic dystrophy.

The present invention is related to a method for treating cancer by using siRNA nanocomplex consisting of a nucleic acid molecule, a monocationic drug and a biocompatible polymer surfactant. The present nanocomplex can deliver an active ingredient (for example, a nucleic acid molecule and monocationic drug) into a cell/tissue of interest in a stable manner, and may be effectively applied for treating or detecting diverse disorders (practically, cancers).

In some aspects, fusosome compositions and methods are described herein that comprise membrane enclosed preparations, comprising a fusogen. In some embodiments, the fusosome can the target cell, thereby delivering complex biologic agents to the target cell cytoplasm.

The emergence of cells with drug resistant and/or stem cell features might explain frequent relapses and the poor outcome of patients with acute myeloid leukemia (AML). LSCs are heterogeneous for their phenotypes and their sensitivity to chemotherapeutic agents in vivo. Using in silico and functional approaches, the inventors uncovered that CALCRL is overexpressed in LSCs compared with normal hematopoietic cells. They further demonstrated that the CALCRL ligand adrenomedullin (ADM) is highly expressed in AML cells and that increased transcript level was markedly associated with decreased complete remission rates, 5-year overall and event7free survival. The inventors also showed that CALCRL depletion strongly affected leukemic growth in vivo and increased mice survival. Targeting ADM phenocopies the biological and anti-leukemic effects of the CALCRL depletion. These data highlight the critical role of ADM and disclose a promising therapeutic target to specifically eradicate R-LSCs and overcome relapse in AML.

The invention concerns KDM5A inhibitors for use in prevention or treatment of idiopathic inflammatory myopathies such as polymyositis, dermatomyositis, necrotizing autoimmune myopathy, and in particular sporadic inclusion body myositis, and diagnosis of these diseases based on KDM5A expression levels in muscle tissue. The invention further concerns pharmaceutical compositions comprising KDM5A inhibitors for use in prevention or treatment of idiopathic inflammatory myopathies such as polymyositis, dermatomyositis, necrotizing autoimmune myopathy, and in particular sporadic inclusion body myositis.

The disclosure relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the DNAJB 1-PRKAC A fusion gene, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of DNAJB 1-PRKAC A fusion.

The present invention includes a method of increasing, stimulating, inducing, promoting, enhancing or maintaining the genomic stability of a cell of a subject, the method comprising decreasing, reducing, inhibiting, suppressing, limiting or controlling loss of methylation of heterochromatin in the cell and/or modulating heterochromatin dysfunction in a cell of a subject, the method comprising activating, eliciting, stimulate ng, inducing, promoting, increasing or enhancing expression or activity in the cell of one or more DNA methyltransferase (DNMT).

The present invention relates to a double-stranded oligonucleotide capable of inhibiting CTGF expression with a very specific and high efficiency, a double-stranded oligonucleotide structure and nanoparticles comprising the double-stranded oligonucleotide, and a use thereof in preventing or treating of fibrotic or respiratory diseases.

Provided are methods, compositions, and cells for use in adoptive cell therapy for the treatment of cancer. The methods involve administering an effective amount of cells to a subject, wherein the cells are modified ex vivo to suppress endogenous Zbtb20 expression and/or activity within the modified cells. The cells may comprise a dominant negative Zbtb20 capable of suppressing endogenous Zbtb20 activity, at least one shRNA capable of suppressing endogenous Zbtb20 expression, or at least one sgRNA capable of suppressing endogenous Zbtb20 expression. The cells may further comprise an exogenous TCR and/or CAR suitable for treating cancer. The method can further involve administering one or more additional cancer therapies, such as cells which express at least one exogenous TCR and/or CAR suitable for treating cancer. The method can provide various advantages, such as a reduction and/or elimination of an amount of cancer cells in the subject.