Factor VIII Sequences

Abstract

There is provided a nucleic acid molecule comprising a nucleotide sequence encoding for a functional factor VIII protein, wherein the portion of the nucleotide sequence encoding for the B domain of the factor VIII protein is between 90 and 111 nucleotides in length and encodes for an amino acid sequence comprising a sequence having at least 85% identity to SEQ ID NO: 4 and which comprises six asparagine residues. Also provided is a functional factor VIII protein, a vector comprising the above nucleic acid molecule, a host cell, a transgenic animal, a method of treating haemophilia, e.g. haemophilia A, and a method for the preparation of a parvoviral gene delivery vector.

1 - 33 . (canceled) 
     
     
         34 . A method of administering to a subject a nucleic acid molecule comprising a nucleotide sequence encoding a Factor VIII protein, wherein the nucleotide sequence is at least 90% identical to SEQ ID NO: 3, wherein the B domain of the Factor VIII protein is replaced with a spacer, and wherein the Factor VIII protein participates in blood coagulation via the coagulation cascade. 
     
     
         35 . The method of  claim 34 , wherein nucleotide sequence encodes a Factor VIII protein comprises an A1, A2, A3, C1 and/or C2 domain having a modified amino acid sequence compared to the wild type amino acid sequence. 
     
     
         36 . The method of  claim 34 , wherein the nucleotide sequence encodes a Factor VIII protein comprises an A2 and A3 domain having a modified amino acid sequence compared to the wild type amino acid sequence. 
     
     
         37 . A method of treating hemophilia comprising administering to a subject a nucleic acid molecule comprising a nucleotide sequence encoding a Factor VIII protein, wherein the nucleotide sequence is at least 90% identical to SEQ ID NO: 3, wherein the B domain of the Factor VIII protein is replaced with a spacer, and wherein the Factor VIII protein participates in blood coagulation via the coagulation cascade. 
     
     
         38 . The method of  claim 37 , wherein nucleotide sequence encodes a Factor VIII protein comprises an A1, A2, A3, C1 and/or C2 domain having a modified amino acid sequence compared to the wild type amino acid sequence. 
     
     
         39 . The method of  claim 34 , wherein the nucleotide sequence encodes a Factor VIII protein comprises an A2 and A3 domain having a modified amino acid sequence compared to the wild type amino acid sequence.