Recent advances in genetically modified large-animal models of human diseases

Large-animal models show greater advantages than rodents in recapitulating human genetic diseases, primarily because of their higher similarity to humans in terms of anatomy, physiology and genetics. Notably, as genome-editing technologies have rapidly improved, particularly transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 (CRISPR-associated protein 9) systems, their application in biomedical research has accelerated. A variety of genetically modified large-animal models, including non-human primates, pigs, dogs, bovines and sheep, have been produced to recapitulate human inherited disorders, thus providing novel biological and translational insights. Here, we review recent progress in the generation of large-animal models over the past 5 years and summarize their use in studying human genetic diseases, focusing on the nervous system, cardiovascular and metabolic systems, the immune system, xenotransplantation, the reproductive system and embryonic development.