Granted Patent
B2
US 12,612,647 · App. 18/154,096 · Granted Apr 28, 2026
Compositions useful in treatment of spinal muscular atrophy
Inventors:
James M. Wilson (Philadelphia, PA); Christian Hinderer (Baltimore, MD); Nathan Katz (Milton, DE); Qiang Wang (Philadelphia, PA)
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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.
Claims (11)
1 . A production cell in culture comprising:
(a) an AAVhu68 VP1 nucleic acid sequence of SEQ ID NO: 7 or a sequence at least 99% identical thereto encoding a AAVhu68 VP1 protein of SEQ ID NO: 8, operably linked to a regulatory sequence which directs expression of AAVhu68 VP1, VP2 and VP3 proteins which assemble into an AAVhu68 capsid in the production cell;
(b) a nucleic acid molecule comprising a vector genome for packaging into the AAVhu68 capsid comprising: an AAV 5′ inverted terminal repeat (ITR) sequence, a CB7 promoter comprising a human cytomegalovirus immediate early enhancer, a chicken beta actin promoter, an intron, a coding sequence for spinal motor neuron 1 (SMN1) isoform D which is SEQ ID NO: 1, a polyA, and an AAV 3′ ITR; and
(c) AAV rep functions and helper functions necessary for packaging of the vector genome of (b) into the AAVhu68 capsid in the production cell to provide a recombinant AAV vector having the vector genome comprising the SMN1 coding sequences in the AAVhu68 capsid.
2 . The production cell according to claim 1 , wherein the AAV helper functions comprise a nucleic acid molecule containing a coding sequence for one or more of adenovirus E1, adenovirus E2a, adenovirus VA, and/or adenovirus E4.
3 . The production cell according to claim 1 , wherein the AAV helper functions comprise a nucleic acid molecule containing a coding sequence for one or more of herpesvirus UL5, herpesvirus UL8, herpesvirus UL52, herpesvirus UL29, and/or herpesvirus polymerase.
4 . The production cell according to claim 1 , wherein the vector genome comprises a 5′ and 3′ AAV ITRs from AAV2 and the cell comprises a nucleic acid molecule encoding rep proteins from AAV2.
5 . The production cell according to claim 1 , wherein the nucleic acid molecule of (b) is a plasmid comprising the vector genome which is packaged into the capsid.
6 . A method for generating a recombinant AAV having an SMN1 gene, said method comprising culturing a production cell according to claim 1 .
7 . A method for generating a recombinant AAV having an SMN1 gene, said method comprising culturing a production cell according to claim 2 .
8 . A method for generating a recombinant AAV having an SMN1 gene, said method comprising culturing a production cell according to claim 5 .
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jan 27, 2023
From: WILSON, JAMES M.; HINDERER, CHRISTIAN; KATZ, NATHAN; WANG, QIANG
To: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Reel/Frame 062505/0027 →
Continuity (5)
Continuation
16487690
Provisional Application
62464756
· Feb 28, 2017
Provisional Application
62515902
· Jun 6, 2017
Provisional Application
62618437
· Jan 17, 2018
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