Robust Heterochiral Strand Displacement Using Leakless Translators
Robust Heterochiral Strand Displacement Using Leakless Translators
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DOI：
10.1021/acssynbio.0c00131
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发表时间：
2020-07-17
影响因子：
4.7
通讯作者：
Lakin, Matthew R.
中科院分区：
文献类型：
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作者：
Mallette, Tracy L.;Stojanovic, Milan N.;Lakin, Matthew R.
分子计算为纳米尺度的原位生物传感和信号处理提供了一个强大的框架。然而，在体内应用中，由于核酸酶对电路元件的降解作用，使用传统的 DNA 元件可能会产生假阳性信号。在这里，我们使用由 L 核酸结构域和 D 核酸结构域组成的混合手性分子来实现无泄漏信号转换器，使 D 核酸信号能够通过杂交被检测到，然后转换成稳健的 L-DNA 信号供进一步分析。我们的研究表明，得益于电路级的鲁棒性，即使 D-DNA 成分被核酸酶降解，我们的系统也不会出现假阳性信号。因此，这项工作拓宽了基于 DNA 的分子计算机在实际体内应用的范围和适用性。
Molecular computing offers a powerful framework for in situ biosensing and signal processing at the nanoscale. However, for in vivo applications, the use of conventional DNA components can lead to false positive signals being generated due to degradation of circuit components by nuclease enzymes. Here, we use hybrid chiral molecules, consisting of both L- and D-nucleic acid domains, to implement leakless signal translators that enable D-nucleic acid signals to be detected by hybridization and then translated into a robust L-DNA signal for further analysis. We show that our system is robust to false positive signals even if the D-DNA components are degraded by nucleases, thanks to circuit-level robustness. This work thus broadens the scope and applicability of DNA-based molecular computers for practical, in vivo applications.