Application of Genetically Engineered Pigs in Biomedical Research

Abstract

Progress in genetic engineering over the past few decades has made it possible to develop methods that have led to the production of transgenic animals. The development of transgenesis has created new directions in research and possibilities for its practical application. Generating transgenic animal species is not only aimed towards accelerating traditional breeding programs and improving animal health and the quality of animal products for consumption but can also be used in biomedicine. Animal studies are conducted to develop models used in gene function and regulation research and the genetic determinants of certain human diseases. Another direction of research, described in this review, focuses on the use of transgenic animals as a source of high-quality biopharmaceuticals, such as recombinant proteins. The further aspect discussed is the use of genetically modified animals as a source of cells, tissues, and organs for transplantation into human recipients, i.e., xenotransplantation. Numerous studies have shown that the pig (Sus scrofa domestica) is the most suitable species both as a research model for human diseases and as an optimal organ donor for xenotransplantation. Short pregnancy, short generation interval, and high litter size make the production of transgenic pigs less time-consuming in comparison with other livestock species This review describes genetically modified pigs used for biomedical research and the future challenges and perspectives for the use of the swine animal models.

Interneuron origins in the embryonic porcine medial ganglionic eminence

“…The myriad immunoreactive processes that could take place, even in a relatively protected environment such as the central nervous system, remain to be optimized for these types of xenotransplantation studies. We anticipate that future studies will address these factors and perhaps utilize CRISPR-based gene editing technologies (Cowan et al, 2019;Hryhorowicz et al, 2020) to generate donor pig embryos ideally suited to this purpose.…”

“…Most successfully applied to organs, xenotransplantation from pig-to-nonhuman primate (or even pig-to-human) raise the exciting possibility that embryonic porcine tissueperhaps coupled with techniques to genetically modify a donor pig using transgenic or CRISPR/Cas9 technologies (Cowan et al, 2019;Hryhorowicz et al, 2020) -could be a viable source of transplantable pallial interneurons. These efforts are supported by data showing similarities at the gene and protein level between humans and pigs (Sjöstedt et al, 2020).…”

CRISPR/Cas Technology in Pig-to-Human Xenotransplantation Research

“…Large animal models could be obtained by microinjection of modifying constructs/RNPs of the CRISPR/Cas system or somatic cell nuclear transfer (SCNT) procedure. We detailed the advantages and disadvantages of these methods in our recent article [ 52 ]. Workflows of both methods are presented in Figure 2 .…”

“…The domestic pig ( Sus scrofa f. domestica ) is currently considered to be the most suitable candidate species. The reasons for selecting a pig as a donor animal include the relatively large litter size and short maturation period, the size and physiological similarity of its organs to human organs, and the low risk of xenozoonosis transmission [ 52 , 61 ]. However, there are discrepancies between pigs and humans which lead to the development of immune barriers that prevent a direct xenotransplantation.…”

Combined Chaetocin/Trichostatin A Treatment Improves the Epigenetic Modification and Developmental Competence of Porcine Somatic Cell Nuclear Transfer Embryos

“…SCNT has applications in many areas, including animal husbandry, biomedical research, and endangered animal conservation (Yang et al, 2007). Recently, the application of SCNT combined with genome editing technique has been attracting attention as an efficient method to produce transgenic animals (Hryhorowicz et al, 2020). In particular, pigs serve as excellent experimental models for biomedical research in areas such as human disease, bioreactors, and xenotransplantation due to anatomic, physiologic and genetic similarities between pigs and humans (Simon and Maibach, 2000;Prather et al, 2003;Schook et al, 2008;Giraldo et al, 2012).…”