[Animal Modeling] - Application Progress of Targeted Gene Modification Technology in Immunodeficiency Animal Model Research

  Immune deficiency animal models have important applications in human related disease mechanism research, drug development, organ transplantation research, and stem cell research. However, due to the difficulty and low efficiency of traditional gene modified animal construction techniques, there are still few immune deficient animal models obtained in medium-sized and large animals. In recent years, emerging targeted gene modification technologies, including ZFNs, TALENs, CRISPR/Cas9, etc., have provided a technical foundation for the construction of efficient immunodeficiency animal models. This article provides an overview of the technical principles and research progress of ZFNs, TALENs, and CRISPR/Cas9, and elaborates in detail on the progress made by these technologies in constructing immune deficient animal models in medium and large animals, including KO Rag1/Rag2 rabbits, KO Rag1/Rag2 pigs, KO IL2rg pigs, and KO Ppar- γ/ Rag1 Monkey and others. These immunodeficient animal models can not only be used for human SCID related disease research, evaluating the efficiency and safety of stem cell transplantation, but also for preclinical surgical treatment research, producing humanized animal models, etc., thereby bridging the gap between experimental animals and medical applications, and promoting the development of a comprehensive evaluation system for preclinical cell regeneration strategies.