The present invention provides for the intratumoral delivery of at least one immunostimulatory cytokine in combination with at least one checkpoint inhibitor. In particular, it provides delivery of a plasmid encoding the immunostimulatory cytokine using intratumoral electroporation. The checkpoint inhibitor may be administered systemically or encoded on a plasmid and delivered using intratumoral electroporation. The checkpoint inhibitor may be delivered contemporaneously with or after treatment with the immunomodulatory cytokine.

Compositions and methods are provided for treating Leber congenital amaurosis (LCA) in a subject. In one aspect, a recombinant adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding Lebercilin. In another aspect, Lebercilin has an amino acid sequence of SEQ ID NO: 1. In yet another aspect, the nucleic acid molecule has a sequence of SEQ ID NO: 3 or a variant thereof. In desired embodiments, the subject is human, cat, dog, sheep, or non-human primate.

Described herein are expression vectors encoding the Wolbachia protein WalE1. Also described are insects transformed with an expression vector of the present disclosure, and progeny thereof. Also described are methods for improving Wolbachia replication and transmission in its insect host by overexpressing WalE1 in the insect host. Improved Wolbachia replication and transmission provides for insect population control and pathogen resistance in insects, which can reduce disease transmission.

The invention relates to an expression system comprising polynucleotides encoding proteins, wherein the expression system comprises a first polynucleotide encoding at least one protein, peptide or variant thereof, which induces a T cell response, and a second polynucleotide encoding at least one protein, peptide or variant thereof, which induces an anti-pathogenic B cell response. The invention further relates to protein mixtures encoded by the expression system and cells comprising the expression system or the protein mixture and pharmaceutical compositions comprising the expression system or the protein mixture.

The present application discloses anti-NME antibodies and their use in treating or preventing diseases.

A method of preparing a chimeric virus comprising bocavirus capsid protein (VP) and a recombinant adeno-associated (AAV) viral genome, and isolated mutant bocavirus genomes, are provided.

Compositions and methods for gene editing. In some embodiments, a polynucleotide encoding Cas9 is provided that can provide one or more of improved editing efficiency, reduced immunogenicity, or other benefits.

An expression vector containing appropriate mitochondrion-targeting sequences (MTS) and appropriate 3′UTR sequences provides efficient and stable delivery of a mRNA encoding a protein (CDS) to the mitochondrion of a mammalian cell. The MTS and 3′UTR sequences guide the CDS mRNA from the nuclear compartment of the cell to mitochondrion-bound polysomes, where the CDS is translated. This provides an efficient translocation of a mature functional protein into the mitochondria. A method of targeting mRNA expressed in the nuclear compartment of a mammalian cell to the mitochondrion is also provided. The vector and methods can be used to treat defects in mitochondrial function.

The invention relates to an artificial nucleic acid molecule comprising at least one open reading frame and at least one 3′-untranslated region element (3′-UTR element) comprising a nucleic acid sequence which is derived from the 3′-UTR of a FIG4 gene or from a variant of the 3′-UTR of a FIG4 gene. The invention further relates to the use of such an artificial nucleic acid molecule in gene therapy and/or genetic vaccination. Furthermore, the invention relates to the use of a 3′-UTR element comprising a nucleic acid sequence which is derived from the 3′-UTR of a FIG4 gene or from a variant of the 3′-UTR of a FIG4 gene for the stabilization and/or prolongation of protein expression from a nucleic acid sequence comprising such 3′-UTR element.

Disclosed herein are nucleic acid-guided nucleases, guide nucleic acids, and targetable nuclease systems, and methods of use. Disclosed herein are engineered non-naturally occurring nucleic acid-guided nucleases, guide nucleic acids, and targetable nuclease systems, and methods of use. Targetable nuclease systems can be used to edit genetic targets, including recursive genetic engineering and trackable genetic engineering methods.