Humanized model mice by genome editing and engraftment technologies

Abstract

Purpose of review In drug development, non-clinical studies are performed to evaluate the feasibility, iterative testing and safety of a drug. To harness this process, small animal models which are inexpensive, and easy to breed and maintain such as mice and rats are preferred for non-clinical studies. However, humans and these animals share a large portion of genetic makeup, but genetic and physiological gaps are unavoidable. Efforts to address this innate difference between humans and animals have been made by establishing a so called ‘humanized’ mouse. In this review, we summarize the scope of the ‘humanization’ with genome editing technology as well as with cell/ tissue engraftment. Recent findings A specifically targeted genetic manipulation became feasible by the development genome editing technologies including zinc finger nucleases (ZFN), transcription activator-like effector nuclease (TALEN), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology. A humanized animal model can also be generated by engraft human cells or tissues into the corresponding sites of animals. If these two approaches are combined in a synergistic manner, a ‘humanized mouse’ would be better used for non-clinical study in various experimental and clinical realms.