英国牛津大学Julian Savulescu等研究人员合作分析出遗传性多基因编辑的潜力。该项研究成果于2025年1月8日在线发表在《自然》杂志上。

研究人员展示了多基因组编辑理论上可以极大地降低疾病易感性。例如，编辑少量的基因组变异可能会显著改变个体患冠状动脉疾病、阿尔茨海默病、重度抑郁症、糖尿病和精神分裂症的风险。类似地，理论上，多基因编辑可以实现，诸如低密度脂蛋白胆固醇和血压等风险因素的显著变化。

尽管遗传性多基因编辑（HPE）仍然是一个假设性的领域，研究人员进行了计算以讨论其潜在的伦理问题。模型展示了基因编辑在个体层面的潜在积极后果，如何加剧健康不平等。此外，由于单一或多个基因变异可能会增加某些疾病的风险，而降低其他疾病的风险，HPE提出了与基因多效性和遗传多样性相关的伦理挑战。

最后，研究人员提出应从集体主义的角度来审视HPE引发的伦理问题，并考虑到它对个人、家庭、社区和社会的影响。

据了解，在人类胚胎和生殖细胞中的多基因组编辑，预计将在未来三十年内变得可行。最近几本书籍和学术论文已经概述了生殖系基因组编辑引发的伦理问题，以及它可能带来的机遇。迄今为止，研究人员还没有尝试，预测改变与多基因疾病相关的特定变异的后果。

附：英文原文

Title: Heritable polygenic editing: the next frontier in genomic medicine

Author: Visscher, Peter M., Gyngell, Christopher, Yengo, Loic, Savulescu, Julian

Issue&Volume: 2025-01-08

Abstract: Polygenic genome editing in human embryos and germ cells is predicted to become feasible in the next three decades. Several recent books and academic papers have outlined the ethical concerns raised by germline genome editing and the opportunities that it may present1,2,3. To date, no attempts have been made to predict the consequences of altering specific variants associated with polygenic diseases. In this Analysis, we show that polygenic genome editing could theoretically yield extreme reductions in disease susceptibility. For example, editing a relatively small number of genomic variants could make a substantial difference to an individual’s risk of developing coronary artery disease, Alzheimer’s disease, major depressive disorder, diabetes and schizophrenia. Similarly, large changes in risk factors, such as low-density lipoprotein cholesterol and blood pressure, could, in theory, be achieved by polygenic editing. Although heritable polygenic editing (HPE) is still speculative, we completed calculations to discuss the underlying ethical issues. Our modelling demonstrates how the putatively positive consequences of gene editing at an individual level may deepen health inequalities. Further, as single or multiple gene variants can increase the risk of some diseases while decreasing that of others, HPE raises ethical challenges related to pleiotropy and genetic diversity. We conclude by arguing for a collectivist perspective on the ethical issues raised by HPE, which accounts for its effects on individuals, their families, communities and society4.

DOI: 10.1038/s41586-024-08300-4

Source: https://www.nature.com/articles/s41586-024-08300-4