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Implementing complex nucleic acid circuits in living cells

delete2025-05-02
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PRE
AI
J
Jiajia Sun
X
Xiewei Xiong
W
Wu, Zhongdong
W
Wang, Heming
Y
Yang, Lei
X
Xue, Niannian
Y
Yao, Qunyan
S
Song, Guangqi
Z
Zhao, Yicheng
L
Li, Li
W
Wang, Fei
F
Fan, Chunhai
DOI:10.1126/sciadv.adv6512delete
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摘要

摘要

En 中文
合成核酸基计算已在体外展示了复杂的计算能力。然而,将这些电路转化为活细胞仍具挑战性,原因在于其不稳定性和细胞干扰。我们介绍了一种别构链交换(ASE)策略,用于复杂细胞内计算。利用构象协同性来调控链交换,ASE提供了一种模块化平台,用于设计具有灵活可编程性的细胞内电路。我们构建了一种基于ASE的可扩展电路架构,能够执行AND和OR逻辑运算,并可扩展至八输入表达。我们证明,基于ASE的电路可通过AND逻辑计算在哺乳动物细胞中高特异性地检测信使RNA。基于ASE的电路接受信使RNA作为输入的能力,使其能够整合内源性细胞信息以实现高效的多输入信息处理,这通过一个监测关键细胞重编程事件的多输入分子分类器得以证明。将ASE电路重新编程以与CRISPR-Cas9接口,能够实现对Cas9靶向活性的可编程控制,用于基因编辑,突显了它们在推进细胞内生物计算方面的潜力。
Keyword:
DNA NANOTECHNOLOGY
MAMMALIAN-CELLS
COMPUTATION
CONSTRUCTION
TRANSPORT
DESIGN
PROBES

期刊

Science Advances 封面图
Science Advances
IF:
12.5
论文数:
2.1W
被引数:
18.1W

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