Compositions and methods for correcting dystrophin mutations in human cardiomyocytes
AssigneeBoard of Regents, The University of Texas System
InventorsEric N. OLSON, Chengzu LONG
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Abstract
The disclosure provides a method for treating or preventing Duchene Muscular Dystrophy (DMD) in a subject in need thereof, the method comprising administering to the subject a Cas9 nuclease or a sequence encoding a Cas9 nuclease, and a gRNA or a sequence encoding a gRNA, wherein the gRNA targets a splice donor or splice acceptor site of the dystrophin gene. The administering restores dystrophin expression in at least a subset of the subjects cardiomyocytes, and may at least partially or fully restore cardiac contractility.
Claims49
A method for editing a mutant dystrophin gene in a cardiomyocyte, the method comprising contacting the cardiomyocyte with:
- a Cas9 nuclease, or a sequence encoding a Cas9 nuclease, and
- a gRNA, or a sequence encoding a gRNA, wherein the gRNA targets a splice donor or splice acceptor site of the dystrophin gene.
An induced pluripotent stem cell (iPSC) comprising:
- a Cas9 nuclease, or a sequence encoding a Cas9 nuclease, and
- a gRNA, or a sequence encoding a gRNA,
- wherein the gRNA targets a splice donor or splice acceptor site of the dystrophin gene.
A method for treating or preventing Duchene Muscular Dystrophy (DMD) in a subject in need thereof, the method comprising administering to the subject:
- a Cas9 nuclease, or a sequence encoding a Cas9 nuclease, and
- a gRNA, or a sequence encoding a gRNA, wherein the gRNA targets a splice donor or splice acceptor site of the dystrophin gene;
- wherein the administering restores dystrophin expression in at least 10% of the subject's cardiomyocytes.
A method for treating or preventing Duchene Muscular Dystrophy (DMD) in a subject in need thereof, the method comprising:
- contacting an induced pluripotent stem cell (iPSC) with
- a Cas9 nuclease, or a sequence encoding a Cas9 nuclease, and
- a gRNA, or a sequence encoding a gRNA,
- wherein the gRNA targets a splice donor or splice acceptor site of the dystrophin gene;
- differentiating the iPSC into a cardiomyocyte;
- and
- administering the cardiomyocyte to the subject.
Dependencies are inferred from the claim text.