合成生物学 ›› 2023, Vol. 4 ›› Issue (2): 301-317.doi: 10.12211/2096-8280.2022-058
马孟丹1,2,3, 刘宇辰1,2
收稿日期:
2022-10-21
修回日期:
2022-12-29
出版日期:
2023-04-30
发布日期:
2023-04-27
通讯作者:
刘宇辰
作者简介:
基金资助:
Mengdan MA1,2,3, Yuchen LIU1,2
Received:
2022-10-21
Revised:
2022-12-29
Online:
2023-04-30
Published:
2023-04-27
Contact:
Yuchen LIU
摘要:
实时、高效和动态地改变储存在基因组中信息的能力是研究细胞生物学、控制细胞表型、监测疾病发展进程、研究原位生物学的一大技术进步。CRISPR-Cas系统的最新研究进展推动了体内DNA和RNA的精确编辑,复杂多变的基因线路使细胞工程化改造成为可能。DNA具有强大的储存信息的能力,可稳定保存数千年,在体内利用DNA记录分子事件是监测细胞信号变化和协调细胞行为的关键技术,能将细胞的瞬时信号转化为可持续反应,并永久保存下来。利用该技术,研究人员能更深入地了解在健康和疾病状态下从基因型到表型转变、临床中患者的疾病发生和用药反应情况、检测生产生活环境的变化。本文概述了合成生物学在DNA存储和细胞实时监测中的技术和应用,以及CRISPR-Cas系统在活细胞中处理和记录各种信息的优势,最后展望了它们在疾病研究和治疗方面的前景和挑战。
中图分类号:
马孟丹, 刘宇辰. 合成生物学在疾病信息记录与实时监测中的应用潜力[J]. 合成生物学, 2023, 4(2): 301-317, doi: 10.12211/2096-8280.2022-058.
Mengdan MA, Yuchen LIU. Potential application of synthetic biology in disease information recording and real-time monitoring[J]. Synthetic Biology Journal, 2023, 4(2): 301-317, doi: 10.12211/2096-8280.2022-058.
图6
用DNA typewriter进行序列基因组编辑[40](a)Type guide上连续两个编辑序列件的示意图,它随着每个编辑序列的位置移动。DNA带由CRISPR-Cas9靶点(灰色方框)的串联序列组成,除第一个外,所有的靶点在其5′端被截断,因此不起作用。5 bp的插入包括一个2 bp的pegRNA特异条形码以及一个3 bp的key来激活下一个单体。因为基因组编辑在这个系统中是按顺序的,所以记录事件的时间顺序可以简单地通过它们沿着序列的物理顺序来读出。(b)用DNA typewriter引导编辑的示意图,引导编辑识别CRISPR-Cas9目标,并使用pegRNA指定的编辑对其进行修改。对于DNA typewriter,插入编辑序列会在随后的单体上生成新的编辑目标。(c)DNA typewriter顺序记录原理图,单个pegRNA与PE2酶一起,可以是事件驱动或者结构性表达的
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