GENOMIC EDITING OF GENES INVOLVED IN CARDIOVASCULAR DISEASE
First Claim
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1. A genetically modified animal comprising at least one edited chromosomal sequence encoding a protein involved in cardiovascular disease.
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Abstract
The present invention provides genetically modified animals and cells comprising edited chromosomal involved in cardiovascular disease. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. The invention also provides zinc finger nucleases that target chromosomal sequences involved in cardiovascular disease and the nucleic acids encoding said zinc finger nucleases. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for toxicity and other effects.
127 Citations
38 Claims
- 1. A genetically modified animal comprising at least one edited chromosomal sequence encoding a protein involved in cardiovascular disease.
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6. The genetically modified animal of 4, wherein the chromosomal sequence encoding a protein involved in cardiovascular disease is chosen from Cacna1C, Sod1, Pten, Ppar(alpha), ApoE, Leptin, and combinations thereof.
- 14. A non-human embryo, the embryo comprising at least one RNA molecule encoding a zinc finger nuclease that recognizes a chromosomal sequence involved in cardiovascular disease, and, optionally, at least one donor polynucleotide comprising a sequence encoding a protein encoded by the chromosomal sequence involved in cardiovascular disease.
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15. The non-human embryo of 14, wherein the protein encoded by the chromosomal sequence involved in cardiovascular disease is chosen from Cacna1C, Sod1, Pten, Ppar (alpha), ApoE, Leptin, and combinations thereof.
- 18. A genetically modified cell, the cell comprising at least one edited chromosomal sequence involved in cardiovascular disease.
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23. The genetically modified cell 18, wherein the protein encoded by the chromosomal sequence involved in cardiovascular disease is chosen from Cacna1C, Sod1, Pten, Ppar(alpha) Apo E, Leptin, and combinations thereof.
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29. A zinc finger nuclease, the zinc finger nuclease comprising:
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a) a zinc finger DNA binding domain that binds a sequence having at least about 80% sequence identity with a sequence chosen from SEQ ID NOs;
4, 5, 6 and 7.b) a cleavage domain. - View Dependent Claims (30, 31, 32, 33)
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34. A nucleic acid sequence bound by a zinc finger nuclease, the nucleic acid sequence having at least about 80% sequence identity with a sequence chosen from SEQ ID NOs:
- 4, 5, 6 and 7.
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35. A method for assessing the effect of an agent in an animal, the method comprising contacting a genetically modified animal, comprising at least one edited chromosomal sequence encoding a protein involved in cardiovascular disease, with the agent and comparing results of a selected parameter to results obtained from contacting a wild-type animal with the same agent, wherein the selected parameter is chosen from:
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a) rate of elimination of the agent or its metabolite(s); b) circulatory levels of the agent or its metabolite(s); c) bioavailability of the agent or its metabolite(s); d) rate of metabolism of the agent or its metabolite(s); e) rate of clearance of the agent or its metabolite(s); f) toxicity of the agent or its metabolite(s); and g) efficacy of the agent or its metabolite(s). - View Dependent Claims (36, 37, 38)
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Specification