Tailored Pig Models for Preclinical Efficacy and Safety Testing of Targeted Therapies.
Despite enormous advances in translational biomedical research, there remains a growing demand for improved animal models of human disease. This is particularly true for diseases where rodent models do not reflect the human disease phenotype. Compared to rodents, pig anatomy and physiology are more similar to humans in cardiovascular, immune, respiratory, skeletal muscle, and metabolic systems. Importantly, efficient and precise techniques for genetic engineering of pigs are now available, facilitating the creation of tailored large animal models that mimic human disease mechanisms at the molecular level. In this article, the benefits of genetically engineered pigs for basic and translational research are exemplified by a novel pig model of Duchenne muscular dystrophy and by porcine models of cystic fibrosis. Particular emphasis is given to potential advantages of using these models for efficacy and safety testing of targeted therapies, such as exon skipping and gene editing, for example, using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system. In general, genetically tailored pig models have the potential to bridge the gap between proof-of-concept studies in rodents and clinical trials in patients, thus supporting translational medicine.
Gene Center and Center for Innovative Medical Models (CiMM), Ludwig-Maximilians-Universität München, Munich, Germany.
Nikolai
N
Klymiuk
Pathology Science, DSM, Transgenic, AstraZeneca RD, Mölndal, Sweden.
Frank
F
Seeliger
Discovery Sciences, RAD, Transgenic, AstraZeneca RD, Mölndal, Sweden.
Mohammad
M
Bohlooly-Y
Institute of Veterinary Pathology, Center for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
Andreas
A
Blutke
Pathology Science, DSM, Transgenic, AstraZeneca RD, Mölndal, Sweden.
Daniel G
DG
Rudmann
Gene Center and Center for Innovative Medical Models (CiMM), Ludwig-Maximilians-Universität München, Munich, Germany ewolf@lmu.de.
Eckhard
E
Wolf
D000818:Animals; D035843:Biomedical Research; D064113:CRISPR-Cas Systems; D003550:Cystic Fibrosis / Q000235:genetics; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005818:Genetic Engineering; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics; D013552:Swine
CRISPR/Cas; Duchenne muscular dystrophy; cystic fibrosis; disease model; exon skipping; genome editing; pig