Abstract
Recent advances in gene editing technologies and in the application of these technologies to livestock animals have created a wealth of opportunity for improving animal health and well being and thereby the production and sustainability of animal protein productions. I review two technology examples in porcine and bovine systems that Genus is engaged in advancing through development. In porcine, recent published work has demonstrated that a simple edit producing a loss of function variant for the gene product CD163 can produce full resistance to the devastating pig disease porcine reproductive and respiratory syndrome virus (PRRSv) . In cattle, a more subtle edit, involving an edit of the -5 amino acid before the signal cleavage site of the CD 18 gene product from glutamine to glycine has been shown in cell model systems to confer resistance to the Mannheimia haemolytica leukotoxin , hypothesized to improve resilience to bovine respiratory disease (BRD). Among other challenges, the development and successful commercialization of these types of gene editing technologies will require the creation of multiple, consistent, reproducible edits in commercial founder lines of elite genetics. The practical challenges of deploying these technologies in beef, dairy and pork production systems are considered.
Highlights
As noted by other authors the relatively recent emergence of efficient gene editing reagents has created a resurgence in interest in livestock genome engineering[3]
Applications are rapidly advancing in the domain of improving animal health and well-being with published proof of concept results addressing high impact diseases like porcine reproductive and respiratory syndrome virus (PRRSv) in swine[1], and day to day management challenges such as dehorning of dairy cattle[6]
The role of the porcine CD163 gene product in PRRSv infection has been reviewed by Welch and Calvert[12] in 2010
Summary
As noted by other authors the relatively recent emergence of efficient gene editing reagents has created a resurgence in interest in livestock genome engineering[3]. Applications are rapidly advancing in the domain of improving animal health and well-being with published proof of concept results addressing high impact diseases like porcine reproductive and respiratory syndrome virus (PRRSv) in swine[1], and day to day management challenges such as dehorning of dairy cattle[6] In addition to these results there are a number of research efforts ongoing to address multiple livestock health challenges. The uncleaved signal peptide of the bovine CD18 gene has been shown in cell system assays to be required for haemolysis to occur, and restoration of cleavage through engineering the introduction of a Q>G mutation can prevent haemolysis 2 These authors hypothesise that introducing this change into cattle and other ruminants could improve the resilience of livestock to BRD2. Both these examples require further research and development to fully realise their potential in livestock, but in addition to the challenges of advancing these types of technologies at the molecular cellular and organismal levels, several additional systemic challenges have to be overcome for the successful commercialization of these types of technologies in modern livestock production systems
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