Modified E1a regulatory sequences are provided, wherein at least one Pea3 binding site, or a functional portion thereof, is deleted. Also provided are modified E1a sequences that selectively express particular isoforms. Also provided is an E1b-19K clone insertion site. These modified sequences can be used individually, or in combination with one another, to provide tumor-selective expression of proteins.

The disclosure features compositions and methods for the treatment of trinucleotide repeat expansion disorders. The compositions described herein that may be used to treat such disorders include at least one nucleic acid construct comprising a first nucleic acid sequence. In some embodiments, the first nucleic acid sequence encodes a therapeutic protein. In some embodiments, the first nucleic acid sequence encodes a MBNL protein. In some embodiments, the first nucleic acid sequence encodes MBNL1 protein. The composition may comprise at least one nucleic acid construct comprising a second nucleic acid. In some embodiments, the second nucleic acid sequence encodes an interfering RNA construct that suppresses the expression of RNA transcripts containing aberrantly expanded repeat regions. Disclosed herein are also methods of increasing the presence of functional muscleblind-like protein (MBNL) in the nucleus of a cell with expression control in tissue types and methods of treating muscular dystrophy or spliceopathy using the compositions disclosed herein.

The present disclosure provides genetically engineered cells and derivatives thereof, particularly cells and derivatives thereof modified with HLA-E and HLA-G transgenes. Also further provided are related vectors, nuclease complexes, polypeptides, polynucleotides, and pharmaceutical compositions. Methods for treating subjects using the genetically engineered cells and/or pharmaceutical compositions are also provided.

The disclosure provides 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 nucleic acid regulatory elements, methods of employing these regulatory elements, uses of these elements, and expression cassettes and vectors containing these nucleic acid regulatory elements are particularly useful for applications using gene therapy, more particularly endothelial cell-directed gene therapy, and for vaccination purposes.

The present invention provides an expression cassette for a target gene and use thereof. Specifically, the present invention provides an expression cassette having elements such as HCR, DSE, TPL and eMlp, an encoding nucleic acid thereof, an expression vector thereof, a host cell thereof, a pharmaceutical composition thereof, a gene delivery system thereof, and use thereof. The present invention further provides a C1-INH protein-encoding nucleic acid molecule and use thereof.

Methods of modulating expression of a target nucleic acid in a cell are provided including use of multiple orthogonal Cas9 proteins to simultaneously and independently regulate corresponding genes or simultaneously and independently edit corresponding genes.

Provided herein are a nucleic acid construct encoding an anti-VEGF fusion protein, such as an expression vector, as well as recombinant virus such as a recombinant lentivirus and a recombinant adeno-associated virus prepared by the construct. Also provided herein are uses of the fusion protein, the nucleic acid construct, and the recombinant virus in the treatment of age-related macular degeneration (AMD), such as wet AMD.