Compositions Useful in Treatment of Spinal Muscular Atrophy
AssigneeThe Trustees of the University of Pennsylvania
InventorsJames M. Wilson, Christian Hinderer, Nathan Katz, Qiang Wang
Life of this patent
Estimating the term…
Abstract
A rAAV vector is described herein which has an AAVhu68 capsid and at least one expression cassette in the capsid. The at least one expression cassette comprises nucleic acid sequences encoding a functional SMN protein and expression control sequences that direct expression of the SMN sequences in a host cell. Also provided are compositions containing this rAAVhu68.SMN vector and methods of using same for spinal muscular atrophy in a patient.
Claims12
A recombinant adeno-associated virus (rAAV) vector comprising an AAVhu68 capsid which has packaged therein a vector genome comprising an AAV 5′ inverted terminal repeat (ITR), a CB7 promoter comprising a human cytomegalovirus immediate early enhancer and a chicken beta actin promoter, an intron, nucleic acid sequences of SEQ ID NO:1, a polyA, and an AAV 3′ ITR, wherein the AAVhu68 capsid comprises
- a heterogenous population of AAVhu68 vp1 proteins selected from:
- vp1 proteins produced by expression from a nucleic acid sequence which encodes the predicted amino acid sequence of 1 to 736 of SEQ ID NO:8, vp1 proteins produced from SEQ ID NO:
- 7, or vp1 proteins produced from a nucleic acid sequence at least 70% identical to SEQ ID NO:7 which encodes the predicted amino acid sequence of 1 to 736 of SEQ ID NO:8,
- a heterogenous population of AAVhu68 vp2 proteins selected from:
- vp2 proteins produced by expression from a nucleic acid sequence which encodes the predicted amino acid sequence of at least about amino acids 138 to 736 of SEQ ID NO:8, vp2 proteins produced from a sequence comprising at least nucleotides 412 to 2211 of SEQ ID NO:7, or vp2 proteins produced from a nucleic acid sequence at least 70% identical to at least nucleotides 412 to 2211 of SEQ ID NO:7 which encodes the predicted amino acid sequence of at least about amino acids 138 to 736 of SEQ ID NO:8, and
- a heterogenous population of AAVhu68 vp3 proteins selected from:
- vp3 produced by expression from a nucleic acid sequence which encodes the predicted amino acid sequence of at least about amino acids 203 to 736 of SEQ ID NO:8, vp3 proteins produced from a sequence comprising at least nucleotides 607 to 2211 of SEQ ID NO:7, or vp3 proteins produced from a nucleic acid sequence at least 70% identical to at least nucleotides 607 to 2211 of SEQ ID NO:7 which encodes the predicted amino acid sequence of at least about amino acids 203 to 736 of SEQ ID NO:8, wherein
- the AAVhu68 capsid is further characterized by having a valine at position 157 and a glutamic acid at position 67.
A host cell comprising:
- (a) a nucleic acid molecule encoding a AAVhu68 VP1 protein;
- (b) a nucleic acid molecule encoding a vector genome comprising:
- an AAV 5′ inverted terminal repeat (ITR) sequence, a CB7 promoter comprising a human cytomegalovirus immediate early enhancer and a chicken beta actin promoter, an intron, nucleic acid sequences of SEQ ID NO:1, a polyA, and an AAV 3′ ITR;
- and
- (c) AAV rep functions and helper functions necessary for packaging and production of a recombinant AAV having an AAVhu68 capsid and the vector genome.
Dependencies are inferred from the claim text.