Gene therapy for lamin a-associated deficiencies
AssigneeThe Trustees of the University of Pennsylvania
InventorChristian Hinderer
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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 expression cassette comprising an open reading frame (ORF) for a mature human Lamin A (hLaminA) under control of a regulatory sequence which direct expression of mature hLaminA 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 treatment of idiopathic dilated cardiomyopathy (DCM) or a disease associated with a mutation in a Lamin A (LMNA) gene.
Claims30
A recombinant adeno-associated virus (rAAV) comprising an adeno-associated virus (AAV) capsid and a vector genome packaged in the AAV capsid, 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 open reading frame (ORF) for mature human Lamin A (hLaminA) coding sequence which encodes for mature hLaminA lacking the preprotein carboxy (C) terminus tail, wherein the ORF is operably linked to regulatory control sequences which direct expression of the mature hLaminA protein in a cell, and wherein the regulatory control sequences comprise a promoter, optionally an enhancer, and a polyadenylation (polyA) sequence.
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16-20. (canceled)
22-28. (canceled)
A recombinant nucleic acid molecule comprising an expression cassette an engineered open reading frame (ORF) for mature human Lamin A (hLaminA), wherein the ORF has a mature hLaminA coding sequence, which is a nucleic acid sequence encoding a functional mature human hLaminA lacking the preprotein carboxy (C) terminus tail, wherein ORF is operably linked to regulatory control sequences, said expression cassette being flanked by a 5′ inverted terminal repeat (ITR) and a 3′ ITR, wherein the engineered hLaminA gene encodes a functional mature hLamin A lacking the preprotein carboxy (C) terminus tail, and wherein the hLaminA coding sequence comprises nucleic acid sequence of SEQ ID NO:
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30-31. (canceled)
A packaging host cell comprising a nucleic acid molecule of claim 31.
33-34. (canceled)
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42-46. (canceled)
Dependencies are inferred from the claim text.