Inducing pluripotency in livestock somatic cells to enhance genome-editing opportunities

Abstract

Although the manipulation of animal genomes has a history of more than three decades, there are only a few of the reported genetically modified (GM) animals that have passed safety regulations and found their way through to market. The production and safety regulations of GM livestock are hindered by a variety of issues, most importantly, lack of embryonic stem cells (ESC) in livestock species and concerns around the nature and biosafety of the genome manipulations, respectively. As an alternative for ESC, induced pluripotent stem cells (iPSC) have reportedly been generated in livestock species. The initial attempts at generating iPSC were based on viral integration of specific factors into the genome of differentiated cells. However, attempts have been made in developing safer methods for generating virus-free iPSC. Although the possibility of inducing a pluripotency state in somatic cells raises hopes to overcome the lack of ESC in livestock, as yet there is no report on successful iPSC cell mediated transgenesis in large domestic animals. Recent advances in genome editing exploiting site-specific endonucleases provide unprecedented potential for modifying the genome of livestock with reduction in off-target events, high efficiency and user-friendly approaches which are widely applicable across species. The high efficiencies achieved support the tantalizing prospect of achieving sophisticated genome-editing at the zygote stage even in livestock species.