Non-human animals comprising a human or humanized IL-4 and/or IL-4Rα nucleic acid sequence are provided. Non-human animals that comprise a replacement of the endogenous IL-4 gene and/or IL-4Rα gene with a human IL-4 gene and/or IL-4Rα gene in whole or in part, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized IL-4 gene under control of non-human IL-4 regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4-encoding sequence with human IL-4-encoding sequence at an endogenous non-human IL-4 locus. Non-human animals comprising a human or humanized IL-4Rα gene under control of non-human IL-4Rα regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4Rα-encoding sequence with human or humanized IL-4Rα-encoding sequence at an endogenous non-human C IL-4Rα locus. Non-human animals comprising human or humanized IL-4 gene and/or IL-4Rα sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.

Provided herein are compositions, methods, and uses involving antibodies that immunospecifically bind glycosylated forms of MUC16, a tethered mucin protein. Also provided herein are uses and methods for managing, treating, or preventing disorders, such as cancer.

Malignant tumors that are resistant to conventional therapies represent significant therapeutic challenges. An embodiment of the present invention provides a new generation regulatable fusogenic oncolytic herpes simplex virus-1 that is more effective at selective killing target cells, such as tumor cells. In various embodiments presented herein, the oncolytic virus described herein is suitable for treatment of solid tumors, as well as other cancers.

Described are receptor ligands of transient receptor potential cation channel subfamily V member 4 (TRPV4), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating ocular disorders.

The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A. In some embodiments, the present disclosure provides methods for dosing a hemophilia A patient with a polynucleotide, e.g., a codon-altered polynucleotide, encoding a Factor VIII polypeptide.

Provided are use of an Echovirus 25 (ECHO25) or a modified form thereof, or a nucleic acid molecule comprising a genomic sequence or cDNA sequence of the ECHO25 or a modified form thereof, or a complementary sequence of the genomic sequence or cDNA sequence, in treatment of a tumor in a subject, and in the manufacture of a medicament for treatment a tumor in a subject.

Tandem gene pairs are described in which the GC3 Content of one gene changes its level of expression, and changes the level of expression of the tandem gene. This gene control is called Mercury and can be used to control the expression level of a gene of interest. Mercury is used herein to reduce tonic signaling from chimeric antigen receptors by reducing the expression of a chimeric antigen receptor.

The invention is in the field of molecular diagnosis of medical diseases and their treatment. More in particular, it provides methods and means for detecting hypertension, more in particular essential primary hypertension, even more in particular NOX5-dependent hypertension. The invention also provides methods for the treatment of hypertension, in particular essential primary hypertension, more in particular NOX5-dependent hypertension. The invention also provides theragnostics, wherein therapy is combined with diagnosis, more in particular wherein the level of NOX5 is determined in a sample from a subject and wherein the subject is treated with NOX5 inhibitors or compounds that decrease the levels of NOX5 if the NOX5 levels are above a certain threshold value. Further, the invention also provides theragnostics, wherein diagnosis is combined with therapy, more in particular wherein the (plasma) level of NOX5 is determined in a sample from a subject and wherein the subject is treated with NOX5 inhibitors or compounds that reverse the result of NOX5 activity in the subject, when the determined NOX5 level is exceeding a predetermined threshold level. Finally, the invention relates to an animal model suitable for developing diagnostic methods and therapeutic treatments for NOX5-dependent hypertension.

The disclosure provides gene therapy vectors, such as adeno-associated virus (AAV), optimized for delivering a transgene to muscles. The optimized vectors contain constitutive or a muscle-specific promoter to deliver whole body or skeletal/heart muscle-specific transgene expression, respectively, in combination with a transgene cDNA to replace the gene mutation found in a muscle disease with a normal copy of the gene, an internal ribosomal entry site (IRES) to allow for production of a second protein from the same transcript, and a muscle growth factor, to build new muscle growth and strength. For example, the invention provides The disclosure provides gene therapy vectors, such as recombinant adeno-associated vims (rAAV), designed for treatment of GNE myopathy in which the rAAV expresses UDP-GlcNAc-epimerase/ManNAc-6 alone or in combination with a muscle growth factor or muscle transdifferentation factor. The provided AAV replace the mutated GNE gene expression while expressing proteins that stimulate muscle growth.

The application relates to the use of loaded red blood cells (e.g. “RBCs”, “red cells” or “erythrocytes”) or red blood cell precursors to produce red cell extracellular vesicles (RCEVs) containing cargos, including cargos comprising biologically active ingredients. Notable red cell precursors include hematopoietic stem cells (HSCs), induced pluripotent stem cells (iPSCs), and reticulocytes. The cargo may comprise nucleic acids, proteins, small molecules, or components of a gene editing system, including CRISPR/Cas9. The RCEVs may be used to treat of diseases and disorders including autoimmune disorders, cancers, cardiovascular diseases, gastrointestinal diseases, genetic disorders, or inflammatory diseases. The RCEVs may also be used to carry antigens and or immune modulator, for use in eliciting immune or immune tolerance responses. Also provided are methods for producing cargo loaded RCEVs (CLRCEVs) by first loading cargo into red cells and then by vesiculating the cargo loaded red cells to yield the CLRCEVs.