Among other things, the present disclosure provides oligonucleotides, compositions, and methods thereof. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., knockdown ability, stability, delivery, etc. In some embodiments, the oligonucleotides decrease the expression, activity and/or level of a C9orf72 gene, including but not limited to, one comprising a repeat expansion, or a gene product thereof. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions, for example, in treatment of C9orf72-related disorders.

The invention relates to the treatment of genetic dilated cardiomyopathies using expressible modulators of the Wnt pathway or TGF-β pathway, preferably using gene transfer.

The present invention relates to a pharmaceutical composition comprising an agent inhibiting gene expression or protein activity of osteopontin as an active ingredient for preventing or treating neurodegenerative disease. According to the present invention, there is an effect of suppressing amyloid beta (Aβ)-induced neuronal cell death by downregulating the expression or activity of osteopontin. In addition, an inhibitor against the expression or activity of osteopontin decreases a level of pro-inflammatory proteins and conversely, increases a level of anti-inflammatory proteins. Therefore, it is expected that the present invention can be advantageously used as a therapeutic agent for various neurodegenerative diseases including Alzheimer's disease.

Provided herein are, inter alia, nucleic acid compounds useful for targeting CTLA-4-expressing cells and modulating cell activity of the CTLA-4-expressing cells. The compositions provided herein may be part of pharmaceutical compositions and may be used for treatment of cancer, inflammatory diseases, infectious diseases or metabolic diseases.

The present disclosure provides methods for genetically modifying lymphocytes and methods for performing adoptive cellular therapy that include transducing T cells and/or NK cells. The methods can include inhibitory RNA molecule(s) and/or engineered signaling polypeptides that can include a lymphoproliferative element, and/or a chimeric antigen receptor (CAR), for example a microenvironment restricted biologic CAR (MRB-CAR). Additional elements of such engineered signaling polypeptides are provided herein, such as those that drive proliferation and regulatory elements therefor, as well as replication incompetent recombinant retroviral particles and packaging cell lines and methods of making the same. Numerous elements and methods for regulating transduced and/or genetically modified T cells and/or NK cells are provided, such as, for example, those including riboswitches, MRB-CARs, recognition domains, and/or pH-modulating agents.

Provided herein are methods and compositions related to treating a hemoglobinopathy. Also provided herein a gene therapeutics for the treatment of hemoglobinopathies and the induction of fetal hemoglobin (HbF).

Provided are methods for editing RNA by introducing a deaminase-recruiting RNA in a host cell for deamination of an adenosine in a target RNA, deaminase-recruiting RNAs used in the RNA editing methods, compositions and kits comprising the same.

Disclosed herein is a composition for gene delivery which forms into liquid crystals in an aqueous fluid including chitosan and a liquid crystal formation material. The composition of the present invention including chitosan and a liquid crystal formation material improves the relatively low binding strength between chitosan and a gene, and also considerably increases the stability of a chitosan nanocomposite in blood serum, thereby performing highly efficient gene delivery and providing excellent stability, thus being useful as a gene therapeutic agent.

In the present specification, on the basis of the correlation between prospero homeobox protein 1 (PROX1) and telomerase reverse transcriptase (TERT), a composition for regulating expression of TERT, a method for screening a TERT expression regulator, a composition for diagnosing a TERT expression status, a diagnostic kit, a method for providing information for diagnosis, or a method for providing information for cancer diagnosis are disclosed. Specifically, in one aspect, the PROX1 of the present disclosure may bind to a TERT promoter, in particular a mutant TERT promoter in which base substitution occurs at the -124 or -146 bp position to regulate the expression of TERT, and the expression of TERT in non-hepatitis B virus-associated liver cancer can be inhibited specifically among liver cancers.

A trans-splicing ribozyme capable of splicing a rhodopsin transcript at a target splicing site and containing a sequence that is capable of complementarily binding to a target binding site of the rhodopsin transcript is disclosed. The trans-splicing ribozyme may further containing a desired rhodopsin transcript at 3′-end. The trans-splicing ribozyme may further contains an antisense sequence that is complementary to a region downstream the target binding site of the rhodopsin transcript. A nucleotide molecule encoding the trans-splicing ribozyme is also disclosed. Delivery systems to delivery the nucleotide molecule and/or the trans-splicing ribozyme to target tissue or cells as well as uses of the trans-splicing ribozyme, the nucleotide molecule, delivery systems, or pharmaceutical compositions containing any of them are also disclosed.