GENOMIC EDITING OF GENES INVOLVED IN TUMOR SUPPRESSION IN ANIMALS
First Claim
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1. A genetically modified animal comprising at least one edited chromosomal sequence encoding a protein involved in tumor suppression.
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Abstract
The present invention provides genetically modified animals and cells comprising edited chromosomal sequences involved in tumor suppression. 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 sequence involved in tumor suppression and the nucleic acids encoding the zinc finger nucleases. Also provided are methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences involved in tumor suppression.
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Citations
34 Claims
- 1. A genetically modified animal comprising at least one edited chromosomal sequence encoding a protein involved in tumor suppression.
- 14. A non-human embryo, the embryo comprising at least one RNA molecule encoding a zinc finger nuclease that recognizes a chromosomal sequence encoding a protein involved in tumor suppression, and, optionally, at least one donor polynucleotide comprising a sequence encoding a protein involved in tumor suppression.
- 18. A genetically modified cell, the cell comprising at least one edited chromosomal sequence encoding a protein involved in tumor suppression.
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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 to a sequence chosen from SEQ ID NOs;
3, 4, 5, 6, 7, and 8; andb) a cleavage domain. - View Dependent Claims (30, 31, 32)
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33. A nucleic acid sequence recognized by a zinc finger nuclease, the nucleic acid sequence having at least about 80% sequence identity to a sequence chosen from SEQ ID NOs:
- 3, 4, 5, 6, 7, and 8.
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34. A method for assessing the therapeutic effect and/or toxicity of an agent, the method comprising:
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a) contacting a first genetically modified animal comprising at least one edited chromosomal sequence encoding a protein involved in tumor suppressor with the agent; b) measuring a therapeutic and/or toxicity response in the first animal; and c) comparing the response in (b) to results obtained from a second genetically modified animal comprising the same edited chromosomal sequence encoding a protein involved in tumor suppression, wherein the second animal is not contacted with the agent.
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Specification