Abstract: The present disclosure provides codon optimized Factor VIII sequences, vectors, and host cells comprising codon optimized Factor VIII sequences, polypeptides encoded by codon optimized Factor VIII sequences, and methods of producing such polypeptides.

Abstract: Provided herein is a baculovirus expression vector system for the production of a desired protein. In one aspect, the desired protein is a closed-ended DNA (ceDNA) molecule comprising wild-type and/or truncated inverted terminal repeats derived from a genome of a member of the viral family Parvoviridae.

Abstract: The present disclosure provides nucleic acid molecules comprising a first inverted terminal repeat (ITR), a second ITR, and a genetic cassette encoding a target sequence. In some embodiments, the first ITR and/or the second ITR is an ITR of a non-adeno-associated virus (AAV). Also disclosed are methods of using the nucleic acid molecules in gene therapy applications.

Abstract: A recombinant von Willebrand Factor (VWF) protein comprising one or more mutations and uses thereof are described. A recombinant protein complex comprising a von Willebrand factor sequence and one artificial Factor VIII sequence is described. A recombinant protein complex comprising a Factor VIII sequence and one artificial von Willebrand sequence is described. A recombinant protein complex is described that includes one artificial von Willebrand factor sequence and one artificial Factor VIII sequence. Also described are nucleic acid sequences and a vector encoding a VWF sequence and a pharmaceutical composition for inducing blood clotting that includes a VWF protein.

Abstract: The present disclosure provides nucleic acid molecules comprising a first inverted terminal repeat (ITR), a second ITR, and a genetic cassette encoding a target sequence. In some embodiments, the target sequence encodes a miRNA and/or a therapeutic protein. In certain embodiments, the therapeutic protein comprises a clotting factor, a growth factor, a hormone, a cytokine, an antibody, a fragment thereof, and a combination thereof. In some embodiments, the first ITR and/or the second ITR is an ITR of a non-adeno-associated virus (AAV). The present disclosure also provides methods of treating a metabolic disorder of the liver in a subject comprising administering to the subject the nucleic acid molecule or a polypeptide encoded thereby.