Genetic enhancement: an avenue to combat aging-related diseases.

Life medicine Pub Date : 2022-11-22 eCollection Date: 2022-12-01 DOI:10.1093/lifemedi/lnac054
Yusheng Cai, Zhejun Ji, Si Wang, Weiqi Zhang, Jing Qu, Juan Carlos Izpisúa- Belmonte, Guang-Hui Liu
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Abstract

Aging is a major risk factor for multiple diseases, including cardiovascular diseases, neurodegenerative disorders, osteoarthritis, and cancer. It is accompanied by the dysregulation of stem cells and other differentiated cells, and the impairment of their microenvironment. Cell therapies to replenish the abovementioned cells provide a promising approach to restore tissue homeostasis and alleviate aging and aging-related chronic diseases. Importantly, by leveraging gene editing technologies, genetic enhancement, an enhanced strategy for cell therapy, can be developed to improve the safety and efficacy of transplanted therapeutic cells. In this review, we provide an overview and discussion of the current progress in the genetic enhancement field, including genetic modifications of mesenchymal stem cells, neural stem cells, hematopoietic stem cells, vascular cells, and T cells to target aging and aging-associated diseases. We also outline questions regarding safety and current limitations that need to be addressed for the continued development of genetic enhancement strategies for cell therapy to enable its further applications in clinical trials to combat aging-related diseases.

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基因增强:对抗衰老相关疾病的新途径
衰老是多种疾病的主要危险因素,包括心血管疾病、神经退行性疾病、骨关节炎和癌症。它伴随着干细胞和其他分化细胞的失调,和/或其微环境的损害。补充上述细胞的细胞疗法提供了一种有希望的方法来恢复组织稳态并减轻衰老和衰老相关的慢性疾病。重要的是,通过利用基因编辑技术,可以开发基因增强,这是一种增强的细胞治疗策略,以提高移植治疗细胞的安全性和有效性。在这篇综述中,我们概述并讨论了遗传增强领域的最新进展,包括间充质干细胞、神经干细胞、血管细胞、造血干细胞和T细胞的遗传修饰,以靶向衰老和衰老相关疾病。我们还概述了关于安全性和当前限制的问题,这些问题需要解决,以继续开发细胞治疗的基因增强策略,使其能够在对抗衰老相关疾病的临床试验中进一步应用。
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