Please develop an overall strategy, using concepts learned from "genome editing" lectures, to achieve the goal of genetic engineering of IRGM allele in provided cell lines. A flow chart of experimental procedures, accompanied by detailed description of each step, is necessary. Your approach should be sufficient for you to test the hypothesis. NOTE: please cover topics of Crispr/Cas9, HDR, PAM site, Donor sequence, Detection of Modified Allele, Off-targets, etc. Specifics about microRNA-196 are not essential. Limit your answer to 2 to 3 pages (single-spaced).