Genetic enhancement: an avenue to combat aging-related diseases

Author:

Cai Yusheng123,Ji Zhejun234,Wang Si56,Zhang Weiqi78,Qu Jing234,Belmonte Juan Carlos Izpisúa-9,Liu Guang-Hui1235ORCID

Affiliation:

1. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China

2. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences , Beijing 100101 , China

3. Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101 , China

4. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China

5. Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053 , China

6. Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University , Beijing 100053 , China

7. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing 100101 , China

8. China National Center for Bioinformation , Beijing 100101 , China

9. Altos Labs , San Diego, CA 92121 , USA

Abstract

AbstractAging 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.

Funder

National Key Research and Development Program of China

Chinese Academy of Sciences

CAS Project for Young Scientists in Basic Research

National Natural Science Foundation of China

Program of the Beijing Natural Science Foundation

Tencent Foundation

Publisher

Oxford University Press (OUP)

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