Heterochiral DNA Strand-Displacement Circuits

Heterochiral DNA Strand-Displacement Circuits
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DOI:
10.1021/jacs.7b10038
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发表时间:
2017-12-13
影响因子:
15
通讯作者:
Sczepanski, Jonathan T.
Sczepanski, Jonathan T.
中科院分区:
化学1区
文献类型:
--
作者:
Kabza, Adam M.;Young, Brian E.;Sczepanski, Jonathan T.

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缺乏一种直接的策略将天然D-DNA与其对映体L-DNA寡核苷酸的相反手性连接起来,无法相互形成连续的沃森-克里克碱基对,这在动态DNA纳米技术领域强制采用了“同手性”范式。因此,手性作为核酸的一个关键内在属性,经常被忽视为基于DNA的设备工程的设计元素,潜在地限制了使用这些系统可以实现的行为类型。在这里,我们介绍了一种支点介导的链位移方法,通过非手性中间体在正交DNA对映体之间传递信息,为具有完全界面的D-DNA和L-DNA组分的“异手性”DNA纳米技术打开了大门。利用这种方法,我们展示了几种具有新功能的异手性DNA电路,包括DNA序列信息的自主手性反转和基于手性的计算。此外,我们发现异手性电路可以直接将内源性rna(如microRNAs)与生物正交的L-DNA连接起来,这可能在生物工程和纳米医学中应用。总的来说,这项工作建立了手性作为动态DNA纳米技术工程的设计参数,从而扩展了使用DNA可以实现的结构和行为的类型。
The absence of a straightforward strategy to interface native D-DNA with its enantiomer L-DNA oligonucleotides of opposite chirality are incapable of forming contiguous Watson-Crick base pairs with each other-has enforced a "homochiral" paradigm over the field of dynamic DNA nanotechnology. As a result, chirality, a key intrinsic property of nucleic acids, is often overlooked as a design element for engineering of DNA based devices, potentially limiting the types of behaviors that can be achieved using these systems. Here we introduce a toehold-mediated strand-displacement methodology for transferring information between orthogonal DNA enantiomers via an achiral intermediary, opening the door for "heterochiral" DNA nanotechnology having fully interfaced D-DNA and L-DNA components. Using this approach, we demonstrate several heterochiral DNA circuits having novel capabilities, including autonomous chiral inversion of DNA sequence information and chirality-based computing. In addition, we show that heterochiral circuits can directly interface endogenous RNAs (e.g., microRNAs) with bioorthogonal L-DNA, suggesting applications in bioengineering and nano medicine. Overall, this work establishes chirality as a design parameter for engineering of dynamic DNA nanotechnology, thereby expanding the types of architectures and behaviors that can be realized using DNA.