The invention refers to an oligonucleotide consisting of 10 to 18 nucleotides of selected regions of the TGF-beta2 nucleic acid sequence, which comprises modified nucleotides such as LNA, ENA, polyalkylene oxide-, 2′-fluoro, 2′-O-methoxy and/or 2′-O-methyl modified nucleotides. The invention further relates to pharmaceutical compositions comprising such oligonucleotide, wherein the composition or the oligonucleotide is used in the prevention and/or treatment of a malignant and/or benign tumor, an immunologic disease, fibrosis, or an ophthalmic disease such as dry eye, glaucoma or posterior capsular opacification (PCO).

The invention provides compositions and methods of making and using effector oligonucleotides, including effector oligonucleotides with greater than one mismatch as compared to its target sequence. These effector oligonucleotides are useful for improving the efficiency of genomic editing as well as providing therapeutic benefits to individuals in need thereof.

The present disclosure relates generally to compounds comprising oligonucleotides complementary to a cystic fibrosis transmembrane conductance regulator (CFTR) RNA transcript. Certain such compounds are useful for hybridizing to a CFTR RNA transcript, including but not limited to a CFTR RNA transcript in a cell. In certain embodiments, such hybridization results in modulation of splicing of the CFTR transcript. In certain embodiments, such compounds are used to treat one or more symptoms associated with Cystic Fibrosis.

The present disclosure provides methods related to inhibiting or treating pancreatitis in a subject in need thereof, which include the use of a proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor. The disclosed PCSK9 inhibitors and compositions including them can be used for treatment, inhibition, or prevention of pancreatitis in a subject. Treatment methods can include administering to the subject a therapeutically effective amount of a PCSK9 inhibitor.

One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The sense strand of the dsRNA agent comprises at least one thermally destabilizing nucleotide, and at least one said thermally destabilizing nucleotide occurring at a site opposite to the seed region (positions 2-8) of the antisense strand; and the antisense strand of the dsRNA agent comprises at least two modified nucleotides that provide the nucleotide a steric bulk that is less than or equal to the steric bulk of a 2′-OMe modification, wherein said modified nucleotides are separated by 11 nucleotides in length. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.

The present invention relates to a SEPT9 inhibitor for use in treatment of an HBV infection, in particular a chronic HBV infection. The invention in particular relates to the use of SEPT9 inhibitors for destabilizing cccDNA, such as HBV cccDNA. The invention also relates to nucleic acid molecules which are complementary to SEPT9 and capable of reducing the level of a SEPT9 mRNA. Also comprised in the present invention is a pharmaceutical composition and its use in the treatment of a HBV infection.

The present invention refers to an antisense oligonucleotide comprising 10 to 25 nucleotides, wherein at least one of the nucleotides is modified, and the antisense oligonucleotide hybridizes with a nucleic acid sequence of Programmed Cell Death 1 (PD-5 1) of SEQ ID NO.1, wherein the antisense oligonucleotide inhibits at least 30% of the PDl expression in a cell compared to an untreated cell. The invention further refers to a pharmaceutical composition comprising such antisense oligonucleotide as well as the use of the antisense oligonucleotide or the pharmaceutical composition in a method of preventing and/or treating a malignant tumor, a benign tumor and/or an infectious disease. The antisense oligonucleotide or the pharmaceutical composition is alternatively used for reducing expression of PD-1 in an isolated immune cell in preparation for cell therapy.

The present invention relates to the field of medicine. It relates more particularly to a product suppressing or reducing the expression or activity of the human small nucleolar RNA (snoRNA) of sequence SEQ ID NO: 1 for use as a medicament. The product of the invention is preferably for use for preventing or treating cancer. The description further relates to vectors, cells, vehicles and compositions capable of delivering and expressing a product suppressing or reducing the expression or activity of the human small nucleolar RNA (snoRNA) of sequence SEQ ID NO: 1, and to uses thereof.

Described herein are compositions for targeting and editing genomes. Also described herein are methods for targeting and editing genomes utilizing the compositions in the instant disclosure.

The present invention provides: a prophylactic or therapeutic agent for at least one type of cancer selected from the group consisting of pancreatic cancer, lung cancer, colorectal cancer, cholangiocarcinoma and liver cancer; a prophylactic or therapeutic agent for the aforementioned cancer, which is used in a combination drug in combination with the aforementioned agent; a combination drug comprising the aforementioned agents; and a method for screening for a prophylactic or therapeutic agent for at least one type of cancer selected from the group consisting of pancreatic cancer, lung cancer, colorectal cancer, cholangiocarcinoma and liver cancer. Provided is a prophylactic or therapeutic agent for at least one type of cancer selected from the group consisting of pancreatic cancer, lung cancer, colorectal cancer, cholangiocarcinoma and liver cancer, the agent comprising a substance capable of reducing the expression of MEX3B gene or MEX3B protein or a substance capable of inhibiting MEX3B protein.