The present disclosure features useful compositions and methods to treat repeat expansion disorders, e.g., in a subject in need thereof. In some aspects, the compositions and methods described herein are useful in the treatment of disorders associated with MLH3 activity.

The current disclosure has identified novel developmental, cellular, molecular, and biochemical pathways and developed a unique mouse model which recapitulates age, bicuspid aortic valve-associated, and gender-specific pathological aspects of development and progression of human CAVD, which will be useful in developing novel diagnostic, preventative, and therapeutic strategies for CAVD patients.

Models and methods related to targeting binding immunoglobulin protein (BiP) are described, where the models and methods allow identification and analysis of protein folding and misfolding.

Provided are antibodies, and fragments, derivatives, and nanoparticle conjugates thereof, particularly humanized derivatives thereof, which bind to tumor antigens. Also provided are nucleic acid molecules encoding chimeric antigen receptors (CARs) that bind to tumor antigens, polypeptides and CARs encoded by the nucleic acid molecules, vectors and host cells that include the nucleic acid molecules, methods of making the same, and methods for using the same to generate a persisting population of genetically engineered T cells in a subject, expanding a population of genetically engineered T cells in a subject, modulating the amount of cytokine secreted by a T cell, reducing the amount of activation-induced calcium influx into a T cell, providing an anti-tumor immunity to a subject, treating a mammal having a MUC1-associated disease or disorder, stimulating a T cell-mediated immune response to a target cell population or tissue in a subject, and imaging a MUC1-associated tumor.

An isolated cytotoxic T-lymphocyte (CTL), said CTL being a tolerance inducing cell and substantially depleted of alloreactivity, and wherein said CTL does not comprise a central memory T-lymphocyte (Tcm) phenotype, the CTL being transduced to express a cell surface receptor comprising a T cell receptor signaling module, is disclosed. Methods of generating same and using same are also disclosed.

Provided herein is a recombinant AAV (rAAV) comprising an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5′ inverted terminal repeat (ITR), an engineered nucleic acid sequence encoding a functional hSGSH, a regulatory sequence which direct expression of hSGSH in a target cell, and an AAV 3′ ITR. Also provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treating a human subject diagnosed with MPS IIIA.

This disclosure relates to mRNA therapy for the treatment of glycogen storage disease type 1a, (GSD-Ia), and related symptoms such as hypoglycemia. mRNAs for use in the invention, when administered in vivo, encode human glucose-6-phosphatase (G6Pase or G6PC), and functional fragments and variants thereof. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of G6PC expression and/or activity in subjects. mRNA therapies of the invention further increase the glucose production, and reduce the abnormal accumulation of glycogen and/or glucose-6-phosphate associated with GSD-Ia.

The present application relates to a nucleic acid molecule comprising a first nucleic acid sequence comprising at least a portion of a 5′ untranslated region (5′ UTR) of a carboxylesterase gene and a second nucleic acid sequence encoding a protein of interest, where the second nucleic acid sequence is heterologous to and operatively coupled to the first nucleic acid sequence. Also disclosed are methods of expressing a protein of interest in a target cell, methods of treating subject for cardiac ischemia or hepatic ischemia, and methods of identifying a nucleic acid sequence capable of selectively enhancing translation of a heterologous protein of interest in a target cell.

This invention relates to polynucleotides encoding mini-dystrophin proteins, viral vectors comprising the same, and methods of using the same for delivery of mini-dystrophin to a cell or a subject.

The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a SIN CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing SIN CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.