**3.1 Genetically modified clinically relevant disease large animal models**

Precise and efficient gene-editing technologies enable the generation of tailored large animal models of human diseases that could contribute to the development of new diagnostic tests and therapeutic procedures [35, 46]. Developmental engineering technology has been used to create large animal models. In 1985, Hammer et al. reported genetically engineered livestock animals [47]. In 1997, Petters et al. presented the first transgenic livestock animal disease model, a pig model of retinitis pigmentosa, which expressed a mutated rhodopsin gene [48]. Recent advances in innovative methods, such as intracytoplasmic sperm injection-mediated gene transfer and somatic cell nuclear transfer (SNCT), enabled design-specific animal models, such as "Dolly," a cloned sheep [49]. Since then, many genetically engineered models of human disease have been generated through large animal models. By integrating SNCT technology and recently developed gene-editing platforms, including TALENs and the CRISPR/Cas9 system, even more diverse modifications of the genomes of livestock species will be seen in the future [50–52]. The commonly used SCNT approach allows concurrent production of transgenic animals expressing a marker gene and non-transgenic clone siblings from the same nuclear donor cells. The cloned animals would provide a useful syngeneic transplantation model [53].
