This invention relates to an RNA trans-splicing molecule (RTM) that targets human endogenous retrovirus (HERV) pre-mRNA. The RTM comprises (i) a binding region specific for a HERV pre-mRNA, (ii) a trans-splicing splice domain and (ill) a coding sequence for a suicide protein. The binding region of the RTM binds to HERV pre-mRNA in a cell, such that the coding sequence is trans-spliced through the trans- splicing domain with the HERV pre-mRNA, resulting in a chimeric mRNA causing the suicide protein to be expressed in the cell. RTMs of the invention may be useful in selectively killing cells that express HERV genes, for example cancer cells. RTMs, encoding nucleic acids, methods of treatment and associated methods and uses are provided.

The disclosure provides methods and materials for detecting endogenous IgA antibodies to one or more, or all, of OmpC (ACA), Ki67 (AKiA), TK1, integrin (AINTA) and keratin (AKERA), which are useful to diagnose and distinguish chronic enteropathies, e.g. gastrointestinal neoplasms, e.g., gastrointestinal lymphoma, and, inflammatory conditions, e g inflammatory bowel disease, in felines.

A method is disclosed for decreasing or retarding an increase in the size of a localized or metastatic tumor by using a combination of an immune stimulating cytotoxic gene therapy and immune-checkpoint modulating agent, in conjunction with other therapies, including radiation therapy, chemotherapy, surgery, and immunotherapies.

A method is disclosed for decreasing or retarding an increase in the size of a localized or metastatic tumor by using a combination of an immune stimulating cytotoxic gene therapy and immune-checkpoint modulating agent, in conjunction with other therapies, including radiation therapy, chemotherapy, surgery, and immunotherapies.

The present invention relates to methods for treating prostate cancer patients. It is based, at least in part, on the discovery that approximately 90% of men carrying at least one of the following fusion genes: TRMT11-GRIK2, SLC45A2-AMACR, MTOR-TP53BP1, LRRC59-FLJ60017, TMEM135-CCDC67 and CCNH-C5orf30 experienced prostate cancer recurrence, metastases and/or prostate cancer-specific death after radical prostatectomy (each examples of progressive prostate cancer), while these outcomes occurred in only 36% of men not carrying any of these fusion genes. It is also based, at least in part, on the discovery that a genome editing technique that specifically targets a fusion gene can induce cell death in a cancer cell that carries the fusion gene.

Provided herein are methods and compositions for a suicide gene approach comprising an expression vector comprising a cell cycle-dependent promoter driving the expression of a suicide gene. Also provided herein are methods to render proliferative cells sensitive to a prodrug after transplantation but avoids expression of the suicide gene in post-mitotic cells, such as neurons.

Described herein are chimeric receptors. Chimeric receptors comprise a cytoplasmic domain; a transmembrane domain; and an extracellular domain. In embodiments, the cytoplasmic domain comprises a cytoplasmic portion of a receptor that when activated polarizes a macrophage. In further embodiments, a wild-type protein comprising the cytoplasmic portion does not comprise the extracellular domain of the chimeric receptor. In embodiments, the binding of a ligand to the extracellular domain of the chimeric receptor activates the intracellular portion of the chimeric receptor. Activation of the intracellular portion of the chimeric receptor may polarize the macrophage into an M1 or M2 macrophage.

A delivery system that includes a recombinantly synthesized protein polymer with protease cleavage sites such as matrix metalloproteinase responsive sequences engineered within the protein polymer. The system may be used to treat cancer, wounds, or pathological conditions in other tissues that express excess protease relative to healthy tissue.

Provided is a method for knocking in a gene of interest to a cell. The genome of the cell contains a negative selectable marker, e.g., a thymidine kinase gene flanked by a pair of recombinase recognition sites (RRS), e.g., attP. The method involves introducing into the cell a targeting construct that contains a gene of interest flanked by a second pair of RRS, e.g., attB. The targeting construct also contains in the vector backbone a negative selectable marker, e.g., thymidine kinase gene. When a recombinase recognizing the RRS is expressed, the recombination events between the two pairs of RRS result in the site-specific integration of the gene of interest in the genome of the cell. Upon selection based on the negative selectable marker, the parental cells, cells with undesired integration, e.g., random integration, or the integration of the vector backbone are removed.

The embodiments relate to monoclonal antibodies or fragments capable of binding to a serum form of human TK1 and to kits and methods involving the use of such monoclonal antibodies or fragments.