Methods and compositions for treating glycogen storage diseases
AssigneeUltragenyx Pharmaceutical Inc.
InventorsChristopher Tipper, Kelly Reed Clark, Samuel Wadsworth
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Abstract
This invention provides a variety of novel adeno-associated virus (AAV) vectors for gene therapy applications in the treatment of glycogen storage disease type 1a (GSD-Ia). Disclosed herein are a number of recombinant nucleic acid molecules, vectors and recombinant AAV that incorporate a modified G6PC promoter/enhancer sequence. Utilization of the modified G6PC promoter/enhancer sequence results in enhanced AAV yield and quality when expressed from various host cell platforms. Also provided herein are compositions comprising the novel AAV of the invention and methods of treating GSD-Ia using the same.
Claims15
A recombinant nucleic acid molecule comprising a modified G6PC promoter/enhancer (GPE) sequence, wherein the modified GPE sequence has a deletion of one or more Alu element(s) selected from the group consisting of Alu-1, Alu-2, and Alu-3, wherein:
- the modified GPE sequence comprises the nucleic acid sequence of contiguous nucleotides 146-2123 of SEQ ID NO:
- 1, or the nucleic acid sequence of SEQ ID NO:
- 7, 8, 9, 10, 11, or 12.
A recombinant adeno-associated virus (rAAV) for the treatment of glycogen storage disease type Ia (GSD-Ia), said rAAV comprising an AAV capsid and a vector genome packaged therein, said vector genome comprising:
- (a) an AAV 5′ inverted terminal repeat sequence (ITR) sequence;
- (b) a promoter/enhancer sequence comprising the contiguous nucleotides 146-2123 of SEQ ID NO:
- 1;
- (c) a coding sequence encoding a glucose-6-phosphatase alpha (G6Pase-α);
- and
- (d) an AAV 3′ ITR.
Dependencies are inferred from the claim text.