Animal models of immunodeficiency have important applications in human-related disease mechanism research, drug development, organ transplant research, and stem cell research. However, due to the difficulties and low efficiency of traditional transgenic animals, almost no animal models of immunodeficiency have been obtained in large and medium-sized animals. In recent years, new targeted gene modification technologies including ZFN, TALEN, CRISPR/Cas9, etc. have provided a technical basis for the establishment of highly effective immunodeficiency animal models. This article outlines the technical principles and research progress of ZFN, TALEN and CRISPR/Cas9, as well as the technical progress in the construction of large and medium-sized animal immunodeficiency animal models including KORag1/Rag2 rabbits and KORag1. I will explain in detail. on. /Rag2 pig, KOIL2rg pig, KOPpar-γ/ag1 monkey and other immunodeficiency animal models can be used not only for the research of human SCID-related diseases and the evaluation of the efficiency and safety of stem cell transplantation, but also for preclinical surgical treatment research. The creation of chemical animal models, etc. Promote the development of a comprehensive evaluation system for animal and medical use bridges, preclinical cell regeneration strategies.