| abstract |
The present invention provides Factor VIII polypeptides comprising one or more substitution mutations compared to the corresponding wild-type Factor VIII, wherein the one or more substitution mutations are located at the interdomain interface between the two domains of the Factor VIII polypeptide. Also provided are polynucleotides comprising Factor VIII nucleotide sequences encoding Factor VIII polypeptides of the present invention, recombinant AAV constructs comprising such polynucleotides, AAV viral particles comprising such recombinant AAV constructs, comprising the present invention Compositions of Factor VIII polypeptides, polynucleotides, recombinant AAV constructs or AAV viral particles of the present invention, and the use of Factor VIII polypeptides, polynucleotides, recombinant AAV constructs, AAV viral particles and compositions of the present invention in therapy. |