Compositions and methods for nucleic acid modifications

A system for modifying a first target nucleic acid comprising:

• a) a nuclease comprising an amino acid sequence having 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, greater than 99% or 100% identity to any of SEQ ID NOs:
• 1-1096 or a first nucleic acid sequence encoding the nuclease;
• and
• b) an engineered guide RNA (gRNA) comprising a first region configured to interact with the nuclease and a second region configured to hybridize with a portion of the first target nucleic acid or a second nucleic acid sequence encoding the gRNA.

A method of generating a cell that expresses a recombinant receptor comprising introducing into the cell:

• a nuclease comprising an amino acid sequence having at least 70% identity, at least 80% c identity, at least 90% identity, at least 95% identity or at least 99% identity to any of SEQ ID NOs:
• 1-1096 or a nucleic acid molecule comprising a sequence encoding the nuclease;
• at least one guide RNA (gRNA) complementary to at least a portion of a target nucleic acid or a nucleic acid comprising a sequence encoding the at least one gRNA;
• and
• a nucleic acid encoding the recombinant receptor.

A method modifying a target nucleic acid in a plant comprising providing to the plant, or a plant cell, seed, fruit, plant part, or propagation material of the plant:

• a nuclease comprising an amino acid sequence having at least 70% identity, at least 80% identity, at least 90% identity, at least 95% identity or at least 99% identity to any of SEQ ID NOs:
• 1-1096 or a nucleic acid molecule comprising a sequence encoding the nuclease;
• and
• at least one guide RNA (gRNA) complementary to at least a portion of the target nucleic acid or a nucleic acid comprising a sequence encoding the at least one gRNA.

A method for treating a disease or disorder in a subject comprising administering to the subject in need thereof:

• a cell comprising a recombinant receptor or a nucleic acid encoding the recombinant receptor, the nuclease, or a nucleic acid encoding thereof, and at least one gRNA, or a nucleic acid encoding thereof;
• or
• a nuclease comprising an amino acid sequence having at least 70% identity, at least 80% identity, at least 90% identity, at least 95% identity or at least 99% identity to any of SEQ ID NOs:
• 1-1096 or a nucleic acid molecule comprising a sequence encoding the nuclease;
• and
• at least one guide RNA (gRNA) complementary to at least a portion of a target nucleic acid or a nucleic acid comprising a sequence encoding the at least one gRNA.