title: Meganucleases Revolutionize the Production of Genetically Engineered Pigs for the Study of Human Diseases.
abstract: Animal models of human diseases are critically necessary for developing an in-depth knowledge of disease development and progression. In addition, animal models are vital to the development of potential treatments or even cures for human diseases. Pigs are exceptional models as their size, physiology, and genetics are closer to that of humans than rodents. In this review, we discuss the use of pigs in human translational research and the evolving technology that has increased the efficiency of genetically engineering pigs. With the emergence of the clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated (Cas) protein 9 system technology, the cost and time it takes to genetically engineer pigs has markedly decreased. We will also discuss the use of another meganuclease, the transcription activator-like effector nucleases , to produce pigs with severe combined immunodeficiency by developing targeted modifications of the recombination activating gene 2 (RAG2).RAG2mutant pigs may become excellent animals to facilitate the development of xenotransplantation, regenerative medicine, and tumor biology. The use of pig biomedical models is vital for furthering the knowledge of, and for treating human, diseases.
authors.affiliation: Division of Animal Science, University of Missouri, Columbia, Missouri, USA.
authors.forename: Bethany K
authors.initials: BK
authors.lastname: Redel
authors.affiliation: Division of Animal Science, University of Missouri, Columbia, Missouri, USA National Swine Resource and Research Center, University of Missouri, Columbia, Missouri, USA pratherr@missouri.edu.
authors.forename: Randall S
authors.initials: RS
authors.lastname: Prather
mesh_terms: D000818:Animals; D035843:Biomedical Research; D064113:CRISPR-Cas Systems; D004268:DNA-Binding Proteins; D003851:Deoxyribonucleases; D005818:Genetic Engineering; D006801:Humans; D023421:Models, Animal; D009687:Nuclear Proteins; D013552:Swine / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D003851:Deoxyribonucleases
keywords: CRISPR; meganucleases; pig models; transcription activator–like effector nucleases; zinc finger nucleases; zygote injections