Optimized messenger RNA

A synthetic nucleic acid sequence which encodes a human Factor VIII, wherein at least one non-common codon or less-common codon has been replaced by a common codon encoding the same amino acid residue as the non-common or less-common codon and wherein the synthetic nucleic acid has a continuous stretch of common codons which comprise at least 60% of the codons of the synthetic nucleic acid sequence, and wherein by a common codon is meant the most common codon encoding each particular amino acid residue in highly expressed human genes as shown in FIGS. 14A and 14B.

A synthetic nucleic acid sequence which encodes a human Factor VIII, wherein at least one non-common codon or less-common codon has been replaced by a common codon encoding the same amino acid residue as the non-common or less-common codon and wherein at least 98% or more of the codons in the sequence encoding the Factor VIII are common codons and the Factor VIII is at least 90 amino acid residues in length, and wherein by a common codon is meant the most common codon encoding each particular amino acid residue in highly expressed human genes as shown in FIGS. 14A and 14B.

A synthetic nucleic acid sequence which encodes human Factor IX, wherein at least one non-common codon or less-common codon has been replaced by a common codon encoding the same amino acid residue as the non-common or less-common codon and wherein the synthetic nucleic acid has a continuous stretch of at least 150 codons all of which are common codons, and wherein by a common codon is meant the most common codon encoding each particular amino acid residue in highly expressed human genes as shown in FIGS. 14A and 14B.

A synthetic nucleic acid sequence which encodes human Factor IX, wherein at least one non-common codon or less-common codon has been replaced by a common codon encoding the same amino acid residue as the non-common or less-common codon and wherein the synthetic nucleic acid has a continuous stretch of common codons which comprise at least 60% of the codons of the synthetic nucleic acid sequence, and wherein by a common codon is meant the most common codon encoding each particular amino acid residue in highly expressed human genes as shown in FIGS. 14A and 14B.

A synthetic nucleic acid sequence which encodes human Factor IX, wherein at least one non-common codon or less-common codon has been replaced by a common codon encoding the same amino acid residue as the non-common or less-common codon and wherein at least 98% or more of the codons in the sequence encoding the Factor IX are common codons and the Factor IX is at least 90 amino acid residues in length, and wherein by a common codon is meant the most common codon encoding each particular amino acid residue in highly expressed human genes as shown in FIGS. 14A and 14B.