Nuclear transfer and the development of genetically modified/gene edited livestock

Abstract

The birth and adult development of “Dolly” the sheep, the first mammal produced by transfer of a terminally differentiated cell nucleus into an egg, provided unequivocal evidence of nuclear equivalence among somatic cells. This ground-breaking experiment challenged a long-standing dogma of irreversible cellular differentiation that prevailed for over a century and enabled the development of methodologies for reversal of differentiation of somatic cells, also known as nuclear reprogramming. Thanks to this new paradigm, novel alternatives for regenerative medicine in humans, improved animal breeding in domestic animals and approaches to species conservation through reproductive methodologies have emerged. Combined with the incorporation of new tools for genetic modification, these novel techniques promise to i) transform and accelerate our understanding of genetic diseases and the development of targeted therapies through creation of tailored animal models, ii) provide safe animal cells, tissues and organs for xenotransplantation, iii) contribute to the preservation of endangered species, and iv) improve global food security whilst reducing the environmental impact of animal production. This review discusses recent advances that build on the conceptual legacy of nuclear transfer and - when combined with gene editing - will have transformative potential for medicine, biodiversity and sustainable agriculture. We conclude that the transformative potential of these technologies depends on further fundamental and translational research directed at improving the efficiency and safety of these methods.

Establishment of a male fertility prediction model with sperm RNA markers in pigs as a translational animal model

“…However, it is hard to apply the findings from studies on rodents to humans or other large animals directly for the following reasons: (i) insufficient clinical/phenotypic information; (ii) lack of field/clinical trial; (iii) the high genetic diversity of human and other large animals; and (iv) the genetic differences between rodents and human/large animals. The pig model has high genetic and physiological similarities with humans [ 27 , 44 ] and is a better candidate for reproductive research than rodent model. Recently, Yue et al presented a pig germline genome engineering technique [ 45 ].…”

Progress in Research and Prospects for Application of Precision Gene-Editing Technology Based on CRISPR–Cas9 in the Genetic Improvement of Sheep and Goats

“…Therefore, inhibiting MSTN expression can induce "dual muscle" traits in developed muscle areas, such as the buttocks, shoulders, and legs, providing application value for improving meat quality and increasing the lean meat percentage in livestock. Albertio and Wolf [97] propose using DNA nucleases to apply this phenotype to cattle, sheep, and pigs, promoting meat production performance in livestock and poultry.…”

Dolly at 25… is she ‘… still goin’ strong?’

“…The penultimate article in this series (Alberio & Wolf 2021) returns to the topic of GM livestock, considering further applications in animal breeding and the development of large-animal models for early human development and disease. The prospect of generating embryonic stem cells in farm animals may obviate the need for somatic cells and improve the overall efficiency of GM-livestock production, superseding current zygotic genome-editing approaches.…”