Homologous recombination directed genome editing in eukaryotes

A synthetic nucleic acid comprising:

• a first nucleic acid sequence encoding a codon-Adapted Nuclear Argonaute protein (ANAGO) that is a polypeptide capable of editing a target nucleic acid sequence within a human cell in the presence of a donor nucleic acid without a guide nucleic acid, wherein the ANAGO is species-specific to human, wherein the ANAGO is attached to a nuclear localization signal peptide sequence (NLS);
• wherein the first nucleic acid sequence is produced by modifying a second nucleic acid sequence of a microbial species, and wherein the second nucleic acid sequence comprises a coding region that is capable of encoding a microbial Argonaute protein that has endonuclease activities in a microorganism;
• wherein the modifying comprises replacing microbial preferred codons of the second nucleic acid sequence with codons that have preferential usage in the human cell;
• and
• wherein the first nucleic acid sequence comprises at least 85% identity to the nucleic acid sequence of SEQ ID NO:2;
• SEQ ID NO:3;
• or SEQ ID NO:4.