$8 million grant will support research with genetically modified pigs to study human diseases.
Investigators at the National Swine Resource and Research Center (NSRRC) at the University of Missouri (MU) have become the go-to source for genetically modified pigs used by researchers across the United States to study various diseases that impact humans.
MU has been awarded $8 million from the National Institutes of Health (NIH) to expand the research facility on MU’s campus to keep up with increasing demand for their expertise and speed up the scientific discoveries that can help treat humans who are suffering from the same diseases shown in the genetically modified pigs.
“We undertake projects for things that have failed in studies with mice but are much better suited for pigs. For example, you can’t take a mouse’s heart and transplant it into a human, it’s not going to work, but pigs are far more genetically and physiologically similar to a human, so they are very good biomedical models to study diseases that impact humans. The cardiovascular systems are very similar between pigs and humans, and baby pigs are also great for studying infant nutrition, as their nutritional requirements and the way they absorb nutrients is very similar to humans.”Randall Prather, MU College of Agriculture, Food and Natural Resources.
In total, the NSRRC has made more than 90 different genetic modifications in pigs to study different diseases.
“It is very intellectually stimulating because every few months, we basically get a mini master’s degree in various fields of physiology, and this grant will help us continue this important work,” Prather said. “At heart, I’m a pig reproductive physiologist and I understand early embryo development, and with that basic understanding, we can now make genetic modifications to investigate and address all kinds of diseases.”
The NSRRC has received funding from the NIH for 20 years, and Prather has been at MU for 33 years. With requests for genetically modified pigs constantly coming in from researchers at universities all over the country, including University of California-Los Angeles, Harvard, Duke, Massachusetts Institute of Technology, Louisiana State University, the University of Iowa, and the University of Indiana, the current facility has maxed out its capacity. Construction on the expanded facility, which will have extremely high biosecurity protocols to ensure, for example, safe transfer of organs from pigs to humans and nonhuman primates, is expected to begin in February 2024 and be completed by summer 2025.
While the NSRRC is mainly focused on biomedical research, Prather’s research also has agricultural applications, such as making pigs that are resistant to certain diseases, which has implications for both agriculture and human medicine.
“One example is the only genetically modified pig that has been approved for human consumption, designed for people who suffer from red meat allergy,” Prather said. “We discovered that by knocking out, or disrupting, a gene that produces a specific sugar molecule on the surface of cells within pigs, humans with red meat allergy can eat the genetically modified pork, which is offered on a limited basis in a slaughterhouse in Iowa, without suffering from any digestive issues.”
Prather invented the patent for this technology that is now owned by MU. In January 2022, surgeons in Maryland successfully transplanted a pig heart into a human patient for the first time ever. Prather’s decades worth of research, work with genetically modified pigs and knowledge of pig-to-human organ transplants helped contribute to the historic accomplishment.
“Our goal is to provide resources and knowledge so that others can be successful in helping people,” Prather said. “Our work is a part of medical solutions for people and this expanded facility is crucial because pigs have so much potential for solving real-world problems. We are just one step in the journey, and it is satisfying to be a part of it.”
Advances in Swine Biomedical Model Genomics
As scientists evaluate methods to prevent infectious diseases and test new therapies and vaccines the pig is an ideal choice. Approaches include probing mucosal tissue responses in respiratory 72, reproductive, neurological, and intestinal infections, testing biotherapeutics and drug therapies, probing the effects of disease on development and testing therapies for specific ailments, e.g., asthma. (Advances in Swine Biomedical Model Genomics)
Swine Models in the Design of More Effective Medical Countermeasures Against Organophosphorus Poisoning
Swine present a number of interesting biological and physiological characteristics. Similarities in skin properties with humans have led to extensive in vitro and in vivo studies. There is a specific interest in cardiovascular research, as well as in anaesthesiology and critical care medicine due to common features of swine and human physiology. The benefits of the swine model justify the use of these animals in the design of more effective medical countermeasures against known chemical warfare agents (nerve agents, vesicants and lung damaging agents). Exposure to organophosphorus (OP) pesticides represents a severe health issue in developing countries, while OP intoxication with the more lethal military nerve agents is not only of military concern but also a terrorist threat. (Toxicology)
A Novel Swine Model of Ricin-Induced Acute Respiratory Distress Syndrome
Establishment of a swine model for the in-depth study of the pathological effects of pulmonary exposure to lethal doses of ricin. Research aimed to evaluate new therapeutic options judiciously tailored for effective treatment of ricin-induced pulmonary intoxication, requires the availability of an animal model that lends itself to continuous monitoring of respiratory and hemodynamic parameters. Although recent reports have shown that a mouse model can be utilized for assessment of pulmonary gas exchange and respiratory mechanics following controlled induction of acute respiratory distress syndrome, mechanical ventilation and repeated blood sampling could be carried out in mice for only a very short time. These mice model systems are therefore not amenable with the surveillance of progression of ricin pathology where clinical symptoms can be discerned only many hours after exposure to the toxin and death occurs only within several days. Large animal models are surmised to have greater translational potential because of the ability to determine gas exchange performance, systemic hemodynamics and pulmonary function tests (PFTs), as well as ventilation/perfusion mismatch, over extended periods of time. (Disease Models & Mechanisms)