CRISPR/Cas9及其衍生编辑器在衰老研究中的应用进展

龚仕涛; 王宇; 陈宇庭

doi:10.12211/2096-8280.2021-100

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CRISPR/Cas9及其衍生编辑器在衰老研究中的应用进展

特约评述 | 更新时间：2025-03-20

- CRISPR/Cas9及其衍生编辑器在衰老研究中的应用进展
- Advances in application of CRISPR/Cas9 and its derivative editors in aging research
- 合成生物学 2022年3卷第1期页码：66-77
- 作者机构：
  
  中国科学院深圳先进技术研究院，合成生物学研究所，基因组工程与治疗研究中心，广东深圳 518055
- 作者简介：
  
  [ "龚仕涛（1994—），男，硕士研究生。研究方向为基因组编辑与基因治疗。E-mail：st.gong@siat.ac.cn" ]
  [ "陈宇庭（1992—），男，助理研究员。研究方向为基因编辑与合成生物学。E-mail：chen.yt@siat.ac.cn" ]
- 基金信息：
  
  国家自然科学基金(32101173)
- DOI：10.12211/2096-8280.2021-100
  中图分类号： Q78
- 收稿：2021-10-27，
  
  修回：2022-02-09，
  
  纸质出版：2022-02-28
- 稿件说明：
移动端阅览
龚仕涛，王宇，陈宇庭. CRISPR/Cas9及其衍生编辑器在衰老研究中的应用进展［J］. 合成生物学， 2022， 3（1）： 66-77

GONG Shitao， WANG Yu， CHEN Yuting. Advances in application of CRISPR/Cas9 and its derivative editors in aging research［J］. Synthetic Biology Journal， 2022， 3（1）： 66-77
龚仕涛，王宇，陈宇庭. CRISPR/Cas9及其衍生编辑器在衰老研究中的应用进展［J］. 合成生物学， 2022， 3（1）： 66-77 DOI： 10.12211/2096-8280.2021-100.

GONG Shitao， WANG Yu， CHEN Yuting. Advances in application of CRISPR/Cas9 and its derivative editors in aging research［J］. Synthetic Biology Journal， 2022， 3（1）： 66-77 DOI： 10.12211/2096-8280.2021-100.

摘要

衰老逐渐成为威胁人类健康的重要因素，其中基因突变及其累积是引发衰老的因素之一。基因编辑技术可以纠正或清除错误基因突变，从而具有延缓衰老和治疗衰老相关疾病的潜力。CRISPR/Cas（clustered regularly interspaced short palindromic repeats/CRISPR-associated protein）的基因编辑工具是基于细菌和古细菌获得性免疫系统发明的，已证明可修改多种生物体的基因组。通过对Cas蛋白的定点突变和表达优化改造，可提高CRISPR/Cas系统在靶向位点的编辑效率、保真性及降低其脱靶效应。随后，科学家们发明了许多基于Cas蛋白的编辑器，如碱基编器、引导编辑器、转座/重组酶等。CRISPR/Cas及其衍生的编辑器，可实现多种形式精确的基因修饰，从而满足不同的基因编辑需求。本文主要概述了CRISPR/Cas系统及其种类、Cas9（CRISPR-associated protein 9）蛋白及其变体、基于Cas9蛋白衍生的基因编辑器，并讨论了这些编辑器在衰老及其相关疾病，如早衰综合症、心血管疾病、年龄相关性黄斑变性、神经退行性疾病等方面的应用研究进展。未来，高精确基因编辑器和递送技术的发明，将加速基因编辑技术用于治疗衰老相关疾病和逆转衰老的基础与临床研究，最终实现人类健康衰老。

Abstract

Aging is a complicated process

with aging individuals exhibiting a decline in organ functions and the development of multiple diseases

making it one of major threats to human health. Senescence is often caused by cellular degeneration

which is characterized by morphological and metabolic changes

chromatin remodeling

altered gene expression and a pro-inflammatory phenotype called senescence-associated secretory phenotype (SASP). Moreover

gene mutations and their accumulation are one of the factors triggering aging

and gene editing technology can thus be used to correct or remove erroneous gene mutations

thereby retarding cellular senescence and individual aging as well as treating individual aging-related diseases. Discovered based on the acquired immune system of bacteria and archaea

CRISPR/Cas was initially used to knock out genes

and then its application has been extended to modify the genomes of various organisms. Amino acid mutation and protein structure optimization of Cas protein can not only expand the range of CRISPR/Cas targeted sequence

but also improve its editing efficiency and fidelity to reduce off-target effect. Many Cas protein-based editors

such as base editors

prime editors

transposases/recombinases

have also been invented

which can achieve single-nucleotide editing and integration of large fragments. CRISPR/Cas and its derived editors enable precise gene modifications to meet requirement for editing different genes. In this article

we summarize the CRISPR/Cas system and its types

Cas9 protein and its variants

gene editors derived from Cas9 protein

and discuss their potential applications in treating aging and aging related diseases including progeria syndrome

cardiovascular disease

age-related macular degeneration and neurodegenerative diseases. In the future

the development of gene editing tools with highly targeted editing and low-level off-target and the optimization of delivery methods will accelerate the transfer of the gene editing technology to research and clinical application. Not only can gene editing be used to treat diseases caused by gene mutations

but also become a favorable tool for the treatment of aging and aging related diseases.

关键词

Keywords

references

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