25th ANNIVERSARY OF CLONING BY SOMATIC-CELL NUCLEAR TRANSFER: Nuclear transfer and the development of genetically modified/gene edited livestock.
25th ANNIVERSARY OF CLONING BY SOMATIC-CELL NUCLEAR TRANSFER: Nuclear transfer and the development of genetically modified/gene edited livestock.
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DOI：
10.1530/rep-21-0078
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发表时间：
2021-06-11
期刊：
影响因子：
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通讯作者：
Wolf E
中科院分区：
文献类型：
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作者：
Alberio R;Wolf E
多利绵羊的出生和成年发育提供了明确的证据，证明了体细胞之间的核对等。多利绵羊是通过将末端分化的细胞核移植到卵子中而产生的第一种哺乳动物。这项突破性的实验挑战了一个多世纪以来盛行的细胞分化不可逆转的长期教条，并使逆转体细胞分化的方法得以发展，也被称为核重新编程。由于这一新的范式，出现了人类再生医学的新替代品，改善了家畜的动物繁殖，并通过生殖方法实现了物种保护。这些新技术与新的转基因工具相结合，有望(I)通过创建量身定制的动物模型来改变和加速我们对遗传病的理解和靶向治疗的开发，(Ii)为异种移植提供安全的动物细胞、组织和器官，(Iii)有助于保护濒危物种，以及(Iv)改善全球食品安全，同时减少动物生产对环境的影响。本综述讨论了建立在核移植概念遗产基础上的最新进展，当与基因编辑相结合时，将对医学、生物多样性和可持续农业具有变革潜力。我们的结论是，这些技术的潜力取决于进一步的基础性和转化性研究，旨在提高这些方法的效率和安全性。
The birth and adult development of 'Dolly' the sheep, the first mammal produced by the 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 potential of these technologies depends on further fundamental and translational research directed at improving the efficiency and safety of these methods.