Genome Editing of Pigs for Agriculture and Biomedicine

Abstract

Pigs serve as an important agricultural resource and animal model in biomedical studies. Efficient and precise modification of pig genome by using recently developed gene editing tools has significantly broadened the application of pig models in various research areas. The three types of site-specific nucleases, namely, zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein, are the main gene editing tools that can efficiently introduce predetermined modifications, including knockouts and knockins, into the pig genome. These modifications can confer desired phenotypes to pigs to improve production traits, such as optimal meat production, enhanced feed digestibility, and disease resistance. Besides, given their genetic, anatomic, and physiologic similarities to humans, pigs can also be modified to model human diseases or to serve as an organ source for xenotransplantation to save human lives. To date, many genetically modified pig models with agricultural or biomedical values have been established by using gene editing tools. These pig models are expected to accelerate research progress in related fields and benefit humans.

No excessive mutations in transcription activator-like effector nuclease-mediated α-1,3-galactosyltransferase knockout Yucatan miniature pigs

“…For these reasons, pigs are considered an important animal species not only as an agricultural resource, but also for biomedical applications. Particularly for clinical applications, pigs are considered to be the most suitable source animals for xenotransplantation, to address the lack of human organs for clinical transplantation [11]. However, there are several concerns associated with using pigs for xenotransplantation of organs.…”

“…Pigs are considered important source animals for agricultural applications and clinical xenotransplantation [11]. However, several concerns have been raised regarding pig-to-human immune incompatibility, and controlling the risk of crossspecies transmission of infectious porcine diseases is a major challenge when using pigs, especially for organ xenotransplantation.…”

Genome Editing by Programmable Nucleases and their applications in livestock species

“…Pigs: -The genome editing techniques have been maximally used in pigs (Ryu et al, 2018;Yang and Wu, 2018). Pig resistant against infection with Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) was produced via genetic knockout of the CD163 receptor using cytoplasmic microinjection mediated delivery of CRISPR/Cas9 construct in embryos (Whitworth et al, 2016).…”

Cloned pig fetuses exhibit fatty acid deficiency from impaired placental transport

“…Pig somatic cell nuclear transfer (SCNT) has valuable applications in agriculture, biomedicine, and life science (Matsunari & Nagashima, ; Yang & Wu, ). However, SCNT‐derived cloned pig fetuses frequently exhibit aberrant intrauterine development (Ao et al, ; Ao, Li, et al, ; Chae et al, ; Kim et al, ; Ruan et al, ), leading to high stillbirth occurrence (17–32.8%; Ao, Zhao, et al, ; Estrada et al, ; Huan et al, ; Kurome et al, ; Liu et al, ), congenital malformations (29.5–60.0%; Kurome et al, ; Schmidt, Winther, Secher, & Callesen, ), and neonatal mortality (48.0–74.5%; Ao et al, ; Park et al, ; Schmidt et al, ) in newborn cloned piglets.…”

“…2009; Yang & Wu, 2018). However, SCNT-derived cloned pig fetuses frequently exhibit aberrant intrauterine development (Ao et al, 2017;Chae et al, 2009;Kim et al, 2011;Ruan et al, 2018), leading to high stillbirth occurrence (17-32.8%; Estrada et al, 2007;Huan et al, 2015;Kurome et al, 2013;Liu et al, 2015), congenital malformations (29.5-60.0%; Kurome et al, 2013;Schmidt, Winther, Secher, & Callesen, 2015), and neonatal mortality (48.0-74.5%; Ao et al, 2017;Park et al, 2009;Schmidt et al, 2015) in newborn cloned piglets.…”