Abstract: The present invention relates to regulatory nucleic acid sequences, in particular muscle-specific promoters, elements thereof, and other such nucleic acid sequences, that are capable of enhancing muscle-specific expression of genes. In particular, the invention relates to regulatory nucleic acid sequences capable of enhancing muscle-specific expression but having low liver-specific expression. The invention also relates to expression constructs, vectors and cells comprising such muscle-specific regulatory nucleic acid sequences, and to methods of their use. The regulatory nucleic acid sequences are of particular utility for gene therapy applications, but also find utility in other areas such as bioprocessing and biotechnology.

Abstract: The present invention relates to the use of a regulatory nucleic acid sequences that are able to regulate gene expression in eukaryotic cells and which are responsive to the unfolded protein response (UPR). There are disclosed regulatable introns and UPR-inducible promoters, which are able to regulate gene expression. There are also disclosed recombinant expression constructs comprising such regulatory nucleic acid sequences, whereby expression of the encoded expression product can be induced by invoking the unfolded protein response (UPR) in a eukaryotic cell containing the construct, methods of using such constructs and associated vectors, cells and suchlike.

Abstract: Methods for producing high titer recombinant adeno-associated virus (rAAV) using modified adenovirus-based helper nucleic acids are disclosed.

Abstract: Disclosed herein are codon-optimized nucleic acids encoding a Factor VIII polypeptide. Also disclosed are expression cassettes and expression vectors (e.g., recombinant AAV (rAAV) vectors) that contain the codon-optimized nucleic acids in expressible form. Methods for the treatment of Hemophilia A comprising administering expression vector comprising the codon-optimized nucleic acids (e.g., a recombinant AAV (rAAV) vector) are also disclosed.