Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Department of Laboratory Medicine, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Anal Bioanal Chem. 2018 Nov;410(28):7285-7293. doi: 10.1007/s00216-018-1340-z. Epub 2018 Sep 14.
A molecular beacon (MB) is an oligonucleotide hybridization probe with a hairpin-shaped structure that leads to specific and instantaneous nucleic acid hybridization, enabling a variety of applications. However, integration of additional module sequences interferes with the performance of MBs and increases the complexity of sequence design. Herein, we develop and characterize a toehold integrated molecular beacon (ToMB) strategy for nucleic acid hybridization, where the reaction rate can be flexibly regulated by a target-induced MB conformational switch. Using this basic mechanism, the ToMB is capable of identifying nucleic acids with high specificity and a wider linearity range compared with the conventional molecular beacon system. We further applied the ToMB to the construction of a hybridization chain reaction system and a basic OR logic gate VJHto explore its programmability and versatility. Our results strongly suggest that the novel ToMB can act as a powerful nano-module to construct universal and multifunctional biosensors or molecular computations. Graphical abstract Molecular beacon is employed as a flexible and switchable spacer to control the toehold-mediated strand displacement reaction.
分子信标（MB）是一种具有发夹结构的寡核苷酸杂交探针，导致特定且瞬时的核酸杂交，从而实现各种应用。然而，额外模块序列的整合会干扰 MB 的性能并增加序列设计的复杂性。在此，我们开发并表征了一种用于核酸杂交的引发子整合分子信标（ToMB）策略，其中反应速率可以通过目标诱导的 MB 构象开关来灵活调节。利用这一基本机制，与传统的分子信标系统相比，ToMB 能够以更高的特异性和更宽的线性范围识别核酸。我们进一步将 ToMB 应用于杂交链式反应系统和基本的 OR 逻辑门 VJH 的构建，以探索其可编程性和多功能性。我们的结果强烈表明，新型 ToMB 可以作为一个强大的纳米模块，用于构建通用的多功能生物传感器或分子计算。
