Manufacturing Reusable NAND Logic Gates and Their Initial Circuits for DNA Nanoprocessors

Manufacturing Reusable NAND Logic Gates and Their Initial Circuits for DNA Nanoprocessors
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DOI:
10.1002/chem.202003959
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发表时间:
2020-12-30
影响因子:
4.3
通讯作者:
Kolpashchikov, Dmitry M.
Kolpashchikov, Dmitry M.
中科院分区:
化学2区
文献类型:
--
作者:
Molden, Tatiana A.;Grillo, Marcella C.;Kolpashchikov, Dmitry M.

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基于DNA的计算机可以潜在地分析复杂的生物标记集,从而促进疾病的诊断和治疗。尽管进行了广泛的努力,但DNA处理器尚未开发出来,部分原因是将可用逻辑门集成到电路中的能力受到限制。我们设计了一个NAND门,它是功能完备的逻辑连接件之一。该门的设计避免了茎环折叠的DNA片段,并能够在含RNaseH的缓冲区中重复操作。门的输出可以转化为RNA裂解活性或由脱氧核酶或分子信标探针产生的荧光信号。此外,三条形成NAND门的DNA链通过点击化学进行交联,并在一个简单的程序中进行纯化,该程序允许在16小时内制造出大约10(13)个门,动手时间约为30分钟。两个NAND门可以连接成一个关联,该关联只需添加DNA连接器链即可执行新的逻辑功能。这项工作中开发的方法可能有助于开发生物兼容的DNA逻辑电路,用于生物技术和医疗应用。
DNA-based computers can potentially analyze complex sets of biological markers, thereby advancing diagnostics and the treatment of diseases. Despite extensive efforts, DNA processors have not yet been developed due, in part, to limitations in the ability to integrate available logic gates into circuits. We have designed a NAND gate, which is one of the functionally complete set of logic connectives. The gate's design avoids stem-loop-folded DNA fragments, and is capable of reusable operations in RNase H-containing buffer. The output of the gate can be translated into RNA-cleaving activity or a fluorescent signal produced either by a deoxyribozyme or a molecular beacon probe. Furthermore, three NAND-gate-forming DNA strands were crosslinked by click chemistry and purified in a simple procedure that allowed approximate to 10(13) gates to be manufactured in 16 h, with a hands-on time of about 30 min. Two NAND gates can be joined into one association that performs a new logic function simply by adding a DNA linker strand. Approaches developed in this work could contribute to the development of biocompatible DNA logic circuits for biotechnological and medical applications.