ENGINEERED MEGANUCLEASES SPECIFIC FOR RECOGNITION SEQUENCES IN THE PCSK9 GENE
First Claim
1. An engineered meganuclease that recognizes and cleaves a recognition sequence consisting of SEQ ID NO:
- 4, wherein said engineered meganuclease comprises a first subunit and a second subunit, wherein said first subunit binds to a first recognition half-site of said recognition sequence and wherein said first subunit comprises;
(a) an amino acid sequence having at least 95% sequence identity to residues 7-153 of any one of SEQ ID NOs;
6-14; and
(b) a first hypervariable (HVR1) region having at least 95% sequence identity to an amino acid sequence corresponding to residues 24-79 of any one of SEQ ID NOs;
6-14;
and wherein said second subunit binds to a second recognition half-site of said recognition sequence and wherein said second subunit comprises;
(i) an amino acid sequence having at least 95% sequence identity to residues 198-344 of any one of SEQ ID NOs;
6-14; and
(ii) a second hypervariable (HVR2) region having at least 95% sequence identity to an amino acid sequence corresponding to residues 215-270 of any one of SEQ ID NOs;
6-14.
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Accused Products
Abstract
The present invention encompasses engineered meganucleases which recognize and cleave a recognition sequence within the human PCSK9 gene. The present invention also encompasses methods for using such engineered meganucleases in a pharmaceutical composition and in methods for treating or reducing the symptoms of cholesterol-related disorders, such as hypercholesterolemia. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating cholesterol-related disorders, such as hypercholesterolemia.
2 Citations
50 Claims
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1. An engineered meganuclease that recognizes and cleaves a recognition sequence consisting of SEQ ID NO:
- 4, wherein said engineered meganuclease comprises a first subunit and a second subunit, wherein said first subunit binds to a first recognition half-site of said recognition sequence and wherein said first subunit comprises;
(a) an amino acid sequence having at least 95% sequence identity to residues 7-153 of any one of SEQ ID NOs;
6-14; and(b) a first hypervariable (HVR1) region having at least 95% sequence identity to an amino acid sequence corresponding to residues 24-79 of any one of SEQ ID NOs;
6-14;and wherein said second subunit binds to a second recognition half-site of said recognition sequence and wherein said second subunit comprises; (i) an amino acid sequence having at least 95% sequence identity to residues 198-344 of any one of SEQ ID NOs;
6-14; and(ii) a second hypervariable (HVR2) region having at least 95% sequence identity to an amino acid sequence corresponding to residues 215-270 of any one of SEQ ID NOs;
6-14. - View Dependent Claims (3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 19, 21, 23, 24, 26, 28, 29, 31, 33, 34, 50)
- 4, wherein said engineered meganuclease comprises a first subunit and a second subunit, wherein said first subunit binds to a first recognition half-site of said recognition sequence and wherein said first subunit comprises;
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2. (canceled)
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6. (canceled)
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18. (canceled)
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20. (canceled)
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22. (canceled)
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25. (canceled)
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27. (canceled)
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30. (canceled)
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32. (canceled)
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35-49. -49. (canceled)
Specification