The disclosure provides a method of modifying a PERV-A receptor gene in a cell. The method includes introducing into the cell a nucleic acid sequence encoding a Cas9 protein and a nucleic acid sequence encoding a guide RNA, introducing into the cell a donor nucleic acid sequence, wherein the Cas9 protein and the guide RNA are expressed and co-localize at a genomic site near or in the PERV-A receptor gene and the donor nucleic acid sequence replaces the PERV-A receptor gene by homology directed repair (HDR).