The present invention relates to the field of cancer and inflammation, and in particular methods of monitoring, diagnosis, prognosis, detecting, treating and preventing cancer and inflammation conditions. The use of composition comprises method of monitoring, diagnosis, prognosis, and detecting cancer and inflammation with EN2 and/or SATB2 expression and/or activity. The pharmaceutical composition will further comprise agents that inhibit EN2 and/or SATB2 expression or activity.

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of ATXN3 RNA in a cell or animal, and in certain embodiments reducing the amount of ATXN3 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include motor dysfunction, aggregation formation, and neuron death. Such neurodegenerative diseases include spinocerebellar ataxia type 3 (SCA3).

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of MSH3 RNA in a cell or subject, and in certain instances reducing the amount of MSH3 protein in a cell or subject. These compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a repeat expansion disease. Such symptoms and hallmarks include brain atrophy, muscle atrophy, nerve degeneration, uncontrolled movement, seizure, tremors, muscle weakness, muscle cramping, difficulty swallowing, difficulty speaking, decreased memory, decreased cognition, anxiety, and depression. Non-limiting examples of repeat expansion diseases that benefit from these compounds, methods, and pharmaceutical compositions are myotonic dystrophy (DM1 and DM2), amyotrophic lateral sclerosis, frontotemporal dementia, Huntington's disease, various polyglutamine disorders, Friedrich's ataxia, Fragile X syndrome, or spinocerebellar ataxia (e.g., SCA1, SCA2, SCA3, SCA6, SCAT, SCA8, SCA10, or SCA17).

The disclosure relates, in some aspects, to methods and compositions for production of immunomodulatory compositions. In some embodiments, the disclosure provides host cells which have been treated ex vivo with one or more oligonucleotide agents capable of controlling and/or reducing the differentiation of the host cell. In some embodiments, compositions and methods described by the disclosure are useful as immunogenic modulators for treating cancer.

The present invention provides compositions and methods for treating cancer with peptide nucleic acid agents. In some embodiments, the present invention provides methods and compositions relating to peptide nucleic acid agents that target oncogenes. For example, the present invention provides compositions, including pharmaceutical compositions, comprising agents specific for BRAF V600E inhibition, or fragments or characteristic portions thereof. The present invention further provides various therapeutic and/or diagnostic methods of using BRAF V600E specific peptide nucleic acid agents and/or compositions.

Provided herein are methods, compounds, and compositions for reducing expression of GYS1 in an individual. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a glycogen storage disease or disorder in an individual in need.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The disclosure provides, inter alia, hybridized nucleic acid sequences and compounds comprising Toll-like receptor 9-binding nucleic acid sequences and nucleic acid sequences comprising a microRNA passenger strand sequence hybridized to a microRNA guide strand sequence; pharmaceutical compositions comprising the hybridized nucleic acid sequences and compounds; and the use of the hybridized nucleic acid sequences, compounds, and pharmaceutical compositions to treat medical conditions, such as cancer and inflammatory diseases.

The invention relates to methods, kits, and compositions for reducing the level of or eliminating antimicrobial resistant (AMR) bacteria in situ. The invention encompasses compositions and methods for selectively eradicating antibiotic resistance in bacteria that carry antibiotic resistance genes in the microbiota using packaged phagemids. The microbiota can be intestinal and the packaged phagemids can be administered to a healthy subject or patient, for example, orally, rectally (e.g., in an enema), vaginally, nasally or to the skin. The phagemid encodes a nuclease or other enzyme that genetically modifies the DNA encoding the antibiotic resistance gene so that the bacteria can then be eliminated with the antibiotic.

The present invention provides RNAi agents, e.g., double stranded RNAi agents, that target the transthyretin (TTR) gene and methods of using such RNAi agents for treating or preventing TTR-associated diseases.