Vectors for Liver-Directed Gene Therapy of Hemophilia and Methods and Use Thereof
AssigneeVrije Universiteit Brussel
InventorsThierry Vandendriessche, Marinee Chuah
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Abstract
The present invention relates to vectors containing liver-specific regulatory sequences and codon-optimized factor IX or factor VIII genes, methods employing these vectors and uses of these vectors. Expression cassettes and vectors containing these liver-specific regulatory elements and codon-optimized factor IX or factor VIII genes are also disclosed. The present invention is particularly useful for applications using gene therapy, in particular for the treatment of hemophilia A and B.
Claims40
A vector comprising a nucleic acid expression cassette comprising a liver-specific regulatory element, a promoter, a minute virus of mice (MVM) intron a transgene, preferably a codon-optimized transgene, and a transcriptional termination signal.
The vector according to 4, wherein the B domain of said FVIII is replaced by a linker having SEQ ID NO:16.
A method to obtain levels of factor IX in plasma equal to or higher than the therapeutic concentration of 50 mU/ml or 100 mU/ml in a subject, wherein the transduction of the viral vector into the subject is done at a dose lower than or equal than 6×1011 vg/kg.
The pharmaceutical composition according to claim 39 wherein said treatment results in levels of factor VIII in plasma of the treated subject that are equal to or higher than the therapeutic threshold concentration of 10 mU/ml plasma in a subject.
The pharmaceutical composition according to claim 40, wherein said treatment comprises the transduction of the vector into the subject at a dose lower than or equal than 2.5×1011 vg/kg.
The pharmaceutical composition according to claim 43, wherein said treatment results in levels of factor IX in plasma of the treated subject that are equal to or higher than the therapeutic threshold concentration of 10 mU/ml, 50 mU/ml, 100 mU/ml, 150 mU/ml, or 200 mU/ml plasma in a subject.
The pharmaceutical composition according to claim 43, wherein said treatment comprises the transduction of the vector into the subject at a dose lower than or equal to 2×1011 vg/kg, 6×1011 vg/kg, or 2×1011 vg/kg.
Dependencies are inferred from the claim text.