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US 12,584,131 B2Granted
Methods of gene therapy
AssigneeOregon Health & Science University
InventorsMarkus Grompe, Amita Tiyaboonchai
Life of this patent
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Abstract
Compositions and methods for gene and/or cell editing are provided.
Claims46
A method for selectively amplifying and/or expanding a population of hepatocytes in a subject, the method comprising the steps of:
- a) inhibiting a cytochrome p450 reductase (POR) in a hepatocyte;
- and
- b) administering a protoxin to a subject having a hepatocyte produced by step a), wherein the protoxin is a small molecule,
- wherein step a) comprises i) administering an inhibitory nucleic acid molecule or a nucleic acid molecule encoding the inhibitory nucleic acid molecule to the hepatocyte or subject, wherein said inhibitory nucleic acid molecule is specific for POR;
- or ii) administering Cas9 and a guide RNA (gRNA) specific for the POR gene or a nucleic acid molecule encoding the gRNA to the hepatocyte or subject, wherein said gRNA sequence combines with said Cas9 resulting in cleavage of said POR gene,
- wherein said protoxin is metabolized into a toxin in hepatocytes not produced by step a) in said subject and induces cell death, and
- wherein said protoxin is not converted to a toxic metabolite in hepatocytes produced by step a), thereby allowing for amplification and/or expansion of the hepatocytes within said subject.
4 more elements
A method for selectively amplifying and/or expanding a population of hepatocytes in a subject, the method consisting of the steps of:
- a) inhibiting cytochrome p450 reductase (POR) in a hepatocyte and optionally introducing a transgene into the hepatocyte;
- and
- b) administering acetaminophen to a subject having a hepatocyte produced by step a),
- wherein step a) consists of i) administering an inhibitory nucleic acid molecule or a nucleic acid molecule encoding the inhibitory nucleic acid molecule to the hepatocyte or subject, wherein said inhibitory nucleic acid molecule is specific for POR;
- or ii) administering Cas9 and a guide RNA (gRNA) specific for the POR gene or a nucleic acid molecule encoding the gRNA to the hepatocyte or subject, wherein said gRNA sequence combines with said Cas9 resulting in cleavage of said POR gene;
- and
- wherein said acetaminophen is not converted to a toxic metabolite in hepatocytes produced by step a), thereby allowing for amplification and/or expansion of the hepatocytes within said subject.
4 more elements
Dependencies are inferred from the claim text.