Genetically Engineered Large Animals in Biomedicine

Abstract

Major progress in genetic engineering and genome editing of livestock species has extended their use to biomedical applications, the most notable being tailored large animal models for translational medicine; porcine cells, tissues and organs for xenotransplantation; and production of pharmaceutical proteins in transgenic large animals. The translation of novel discoveries from basic research to clinical application is a long, often inefficient and costly process. Appropriate animal models are critical for the success of translational research. Although rodent models are widely used, they often do not accurately represent the human disease. Thus, additional animal models that more closely mimic aspects of human anatomy and physiology are required. Several genetically engineered pig models have been generated, many of which represent human disease mechanisms and phenotypes more closely than existing rodent models. In addition, genetically modified small ruminants and rabbits are interesting models for specific disease entities. Pigs are the most promising donor species for xenotransplantation. Since multiple genetic modifications are required to prevent immune rejection, to overcome physiological incompatibilities of xeno-organs and to eliminate potential risk factors such as porcine endogenous retroviruses (PERV), genome editing is speeding progress in this field. Last but not least, genetic engineering of large animal species as bioreactors for the production of pharmaceutical proteins is still an interesting option, though only a few such products are on the market. In summary, genetically engineered large animals are playing an increasingly important role in biomedicine. In particular, genetically tailored large animal models may help to bridge the gap between proof-of-concept studies in rodent models and clinical trials in human patients.