In one embodiment, the present disclosure provides an engineered cell having a first chimeric antigen receptor polypeptide including a first antigen recognition domain, a first signal peptide, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and a second chimeric antigen receptor polypeptide including a second antigen recognition domain, a second signal peptide, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain is different than the second antigen recognition domain.

The invention relates to a HLA-B27 Fc open conformer or a HLA-B27 Fc fusion protein for use in the treatment or prevention of cancer. The Fc open conformer comprises or consists of a first and a second monomer, and each monomer comprises a HLA-B27 chain. The Fc fusion protein further comprises a protein stabilizing polypeptide sequence and optionally an amino acid linker. Further aspects of the invention provide combination medicaments comprising the HLA-B27 Fc open conformer and immune checkpoint inhibitors.

Methods for treating or reducing the risk of a cytomegalovirus infection in a subject that include administering one or more of an inhibitor of Deleted in Malignant Brain Tumors 1 (DMBT1), an inhibitor of OR14I1, or an inhibitor of adenylyl cyclases.

The present invention provides, among other things, methods of delivering mRNA in vivo, including administering to a subject in need of delivery a composition comprising an mRNA encoding a protein, encapsulated within a liposome such that the administering of the composition results in the expression of the protein encoded by the mRNA in vivo, wherein the liposome comprises a cationic lipid of formula I-c:

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or a pharmaceutically acceptable salt thereof.

Methods of treating a subject using a T cell therapy are disclosed herein. The methods include increasing BCL11B expression in hematopoietic stem and progenitor cells (HSPCs), pluripotent stem cells, or mature T cells to form modified cells and administering a therapeutically effective amount of the modified cells to the subject for the T cell therapy. BCL11B expression in the HSPCs, pluripotent stem cells, or mature T cells increases production and/or proliferation of T cells from the HSPCs and/or the pluripotent stem cells, and/or increases proliferation of the T cells.

CD47+ disease cells such as cancer cells are treated using a combination of CD47 blockade drug and a proteasome inhibitor. The anti-cancer effect of one drug enhances the 5 anti-cancer effect of the other. Specific combinations include SIRPαFc as CD47 blockade drug, and one of bortezomib, ixazomib and carfilzomib as proteasome inhibitor. These combinations are useful particularly to treat blood cancers including lymphomas, leukemias and myelomas.

Methods and compositions are provided for reducing virus titer and eliminating virus-infected cells from an individual.

Nucleic acid regulatory elements that are able to enhance muscle-specific expression of genes, methods employing these regulatory elements and uses of these elements. Expression cassettes and vectors containing these nucleic acid regulatory elements are also disclosed. The present invention is particularly useful for applications using gene therapy, more particularly muscle-directed gene therapy.

The present disclosure relates generally to the use of sphingolipid-metabolizing proteins to mitigate or minimize tissue damage resulting from injury or from disease, for example, pulmonary arterial hypertension (PAH) when the sphingolipid-metabolizing protein is delivered via expression from an Anc80 vector.

Disclosed are nucleic acid constructs comprising a nucleic acid sequence encoding a vitelliform macular dystrophy-2 (VMD2) promoter operably linked to a nucleic acid sequence encoding Rap1a. Disclosed are vectors comprising the nucleic acid constructs disclosed herein. Disclosed are compositions comprising the disclosed nucleic acid constructs or vectors. Also disclosed are methods of treating a subject having age-related macular degeneration comprising administering one or more of the disclosed nucleic acid constructs, vectors, or compositions to a subject in need thereof.