Gene therapy for treatment of mucopolysaccharidosis iiia
AssigneesThe Trustees of the University of Pennsylvania, Amicus Therapeutics, Inc.
InventorsJuliette Hordeaux, James M. Wilson, Leida Rassouli-Taylor, Hung Do, Steven Tuske
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Abstract
Provided herein is a recombinant AAV (rAAV) comprising an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5′ inverted terminal repeat (ITR), an engineered nucleic acid sequence encoding a functional hSGSH, optionally comprising stabilizing amino acid changes, a regulatory sequence which direct expression of hSGSH in a target cell, and an AAV 3′ ITR. Also provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treating a human subject diagnosed with MPS IIIA.
Claims35
A recombinant adeno-associated virus (rAAV) comprising an adeno-associated virus (AAV) capsid and a vector genome, wherein the vector genome comprises an AAV 5′ inverted terminal repeat (ITR), an expression cassette, and an AAV 3′ITR, wherein the expression cassette comprises an engineered nucleic acid sequence encoding for a functional human N-sulfoglycosamine sulfohydrolase (hSGSH), wherein the hSGSH coding sequence comprises a signal peptide sequence and a mature hSGSH coding sequence, wherein the mature hSGSH coding has the nucleic acid sequence of SEQ ID NO:
- 16 or a nucleic acid sequence which is (a) at least 85% identical to SEQ ID NO:
- 16;
- or (b) at least 99% identical to SEQ ID NO:
- 16, wherein the hSGSH coding sequence is operably linked to regulatory control sequences which direct expression of the hSGSH in a cell.
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A nucleic acid molecule comprising an expression cassette comprising an engineered functional human N-sulfoglycosamine sulfohydrolase (hSGSH) gene and regulatory control sequences, said expression cassette being flanked by a 5′ inverted terminal repeat (ITR) and a 3′ ITR, wherein the engineered hSGSG gene encodes a functional hSGSH, wherein the hSGSH coding sequence comprises a signal peptide sequence and a mature hSGSH, and wherein the mature hSGSH-coding sequence is SEQ ID NO:
- 16.
52-53. (canceled)
Dependencies are inferred from the claim text.