The present invention relates to nucleic acid regulatory elements that are able to enhance endothelial cell-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 endothelial cell-directed gene therapy, and for vaccination purposes.

The invention provides gene therapy vectors, such as adeno-associated virus (AAV) vectors, expressing a functional fragment of the miniaturized human micro-dystrophin gene and method of using these vectors to express the fragment of micro-dystrophin in skeletal muscles including diaphragm and cardiac muscle and to protect muscle fibers from injury, increase muscle strength and reduce and/or prevent fibrosis in subjects suffering from muscular dystrophy.

The invention relates to chimeric AAV capsids targeted to the central nervous system, virus vectors comprising the same, and methods of using the vectors to target the central nervous system. The invention further relates to chimeric AAV capsids targeted to oligodendrocytes, virus vectors comprising the same, and methods of using the vectors to target oligodendrocytes.

Provided herein are methods and compositions for plakophilin-2 gene therapy for treating heart diseases such as arrhythmogenic right ventricular cardiomyopathy (ARVC) or arrhythmogenic cardiomyopathy (ACM).

A synthetic nucleic acid expression system for production of a transcript of interest in a predefined cell-state is provided, the system comprising (a) a first nucleic acid sequence comprising a first promoter operably linked to a nucleic acid sequence encoding a first trans-spliceable pre-mRNA sequence comprising at least one exon encoding a 5′ fragment of said transcript of interest and a first RNA sequence required for spliceosome-dependent trans-splicing; and (b) a second nucleic acid sequence comprising a second promoter operably linked to a nucleic acid sequence encoding a second trans-spliceable pre-mRNA sequence comprising at least one exon encoding a 3′ fragment of said transcript of interest and a second RNA sequence required for spliceosome-dependent trans-splicing; wherein said first promoter and said second promoter are different and each one is specifically regulated by said predefined cell-state.

This invention provides methods and materials for treating cancer. The invention encompasses methods and materials for delivering programmed death-ligand 1 (PD-L1) binding compounds and/or compositions containing one or more monovalent or multivalent programmed death-ligand 1 (PD-L1) binding compounds which are administered to a mammal having cancer to treat the mammal. In some cases, a multivalent PD-L1 binding compound can include two or more programmed cell death protein 1 (PD-1) polypeptides (and/or fragments thereof having the ability to bind PD-L1). This invention also provides methods and materials for making multivalent PD-L1 binding compounds and methods and materials for making nucleic acid molecules that encode PD-L1 binding compounds.

Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.

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 features methods and compositions for expressing transgenes in microglia. The disclosed compositions comprise isolated fragments of human and murine translocator protein (TSPO) promoters and expression cassettes comprising the same. The methods involve using these promoters and/or expression cassettes to express transgenes in a cell.

The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 1400 bp having at least 80% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in cells expressing glial fibrillary acidic protein of a gene when operatively linked to a nucleic acid sequence coding for said gene.