CPC C12N 15/102 (2013.01) [C12N 9/1007 (2013.01); C12N 15/86 (2013.01); C12N 2750/14143 (2013.01)] | 30 Claims |
1. A method of modifying a target locus of interest comprising delivering to said locus:
a) an engineered polypeptide or a nucleic acid encoding the engineered polypeptide, wherein the engineered polypeptide is a variant of the polypeptide according to SEQ ID NO: 3, wherein the variant has reduced nucleic acid cleavage activity relative to the polypeptide according to SEQ ID NO: 3, wherein the variant comprises an amino acid sequence at least 80% identical to SEQ ID NO: 3, and wherein the variant comprises at least one amino acid substitution at a position selected from a group consisting of D326, E422, R490, and D510 of SEQ ID NO: 3; and
b) a guide nucleic acid or DNA molecule encoding the guide nucleic acid, the guide nucleic acid comprising:
i) a first sequence that is bound by the polypeptide, wherein the first sequence comprises a nucleotide sequence that is at least 90% identical to residues 28-37 of SEQ ID NO: 53, and
ii) a second sequence that hybridizes to a target sequence of a target nucleic acid, wherein the first sequence is located 5′ of the second sequence.
|