The present disclosure provides, among other things, a recombinant adeno-associated viral (rAAV) vector encoding an agent that inhibits the proteolytic activity of plasma kallikrein. The disclosure also provides, a recombinant adeno-associated viral (rAAV) vector encoding an anti/plasma kallikrein antibody heavy drain and an anti-plasma kallikrein antibody light chain.

Liver-specific promoters and application thereof are provided. A set of small-size recombinant nucleic acid sequences for regulating high specific expression of genes in a liver system are provided. Compared with the currently reported other sequences of similar size, the said recombinant regulatory sequence fragment has the advantage that the ability of driving expression of reporter gene and human coagulation factor FVIII in the liver system is significantly enhanced, thereby being suitable for recombinant adeno-associated virus (rAAV)-mediated gene therapy.

The present disclosure provides, among other things, a recombinant adeno-associated virus (rAAV) vector comprising an AAV8 capsid and a codon-optimized SERPING1 sequence encoding a human C1-esterase inhibitor. The disclosure also provides a method of treating a subject having Hereditary angioedema (HAE), comprising administering to the subject in need thereof a recombinant adeno-associated virus (rAAV) vector comprising an AAV8 capsid, and codon-optimized SERPING1 sequences encoding a human C1-esterase inhibitor.

Recombinant AAV (rAAV) vectors comprising a rAVV genome comprising a heterologous nucleic acid encoding a lysosomal protein, e.g., acid alpha-glucosidase (GAA) polypeptide, and optionally a signal peptide and/or optionally a targeting sequence, e.g., IGF2 targeting peptide, operatively linked to a liver-specific promoter (LSP), enabling the GAA polypeptide to be secreted from the liver and targeted to the lysosomes. Particular embodiments relate to a recombinant AAV (rAAV) vector encoding an alpha-glucosidase (GAA) polypeptide, having a liver secretory signal peptide and a IGF2 targeting peptide that binds human cation-independent mannose-6-phosphate receptor (CI-MPR) or to the IGF2 receptor, permitting proper subcellular localization of the GAA polypeptide to lysosomes. Also encompassed are cells, and methods to treat a lysosomal disease, for example, a glycogen storage disease type II (GSD II) disease and/or Pompe Disease with the rAAV vector.

Nucleic acids encoding fusion proteins that contain an unwanted antigen and a leader sequence for cell secretion are described. Also described are expression cassettes, vectors, cells, and cell lines containing the nucleic acids, as well as methods of using the nucleic acids to treat autoimmune, allergic and other diseases and disorders, such as multiple sclerosis.

A group of gRNAs is provided, and the group of gRNAs comprises a first gRNA molecule; and a second gRNA molecule capable of defining a region in a genome sequence with the first gRNA molecule, wherein the region in the genome comprises a target sequence in need of removal.

Disclosed herein are methods of repairing or restoring a sarcoglycan complex or DAPC, stabilizing DAPC, restoring DAPC function, or increasing or enhancing expression of one or more components of a sarcoglycan complex or DAPC in a subject suffering from a muscular dystrophy.

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 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 400 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 rod photoreceptors of a gene when operatively linked to a nucleic acid sequence coding for said gene.

Genetically modified mesenchymal stem cells can be used as a medicament in the treatment of medical conditions associated with inflammation and/or an unwanted immune response in subjects without an alpha1-antitrypsin (AAT) deficiency. The stem cells include an exogenous nucleic acid, which includes (i) an Alpha-1 antitrypsin (AAT) encoding region operably linked to (ii) a promoter or promoter/enhancer combination.