Expanding the rule set of DNA circuitry with associative toehold activation.

Expanding the rule set of DNA circuitry with associative toehold activation.
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DOI:
10.1021/ja206690a
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发表时间:
2012-01-11
影响因子:
15
通讯作者:
Chen, Xi
Chen, Xi
中科院分区:
化学1区
文献类型:
--
作者:
Chen, Xi

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支点介导的链置换已被证明在编程无酶DNA电路和DNA纳米机器中非常强大。为了实现多步、自主和复杂的行为,支点必须首先通过与抑制剂链或结构域杂交而失活,然后以编程的定时方式从失活中解脱出来。虽然强大且相当稳健,但这种策略有几个缺点,限制了DNA电路的架构。例如,支点和分支迁移(BM)域之间的组合在DNA合成期间是“硬连线”的,因此在DNA电路的执行期间不能被创建或改变。为了解决这个问题,我提出了一个策略,称为“关联支点激活”,其中支点和BM域连接通过杂交的辅助域在执行DNA电路。在该方案中,稳定DNA 3向连接的凸出胸苷基本上加速链置换反应,允许由可逆立足点结合引发的快速链置换。为了证明该方案的多功能性,我显示(1)运行时的支点和BM域的组合,(2)运行时的支点和BM域的重组,这导致一种新的操作“支点开关”,和(3)一个简单的构象自我复制的设计。
Toehold-mediated strand displacement has proven extremely powerful in programming enzyme-free DNA circuits and DNA nanomachines. To achieve multistep, autonomous, and complex behaviors, toeholds must be initially inactivated by hybridizing to inhibitor strands or domains, and then relieved from inactivation in a programmed, timed manner. Although powerful and reasonably robust, this strategy has several drawbacks that limit the architecture of DNA circuits. For example, the combination between toeholds and branch migration (BM) domains is ‘hard-wired’ during DNA synthesis, thus cannot be created or changed during the execution of DNA circuits. To solve this problem, I propose a strategy called ‘associative toehold activation’, where the toeholds and BM domains are connected via hybridization of auxiliary domains during the execution of DNA circuits. Bulged thymidines that stabilize DNA 3-way junctions substantially accelerate strand displacement reactions in this scheme, allowing fast strand displacement initiated by reversible toehold binding. To demonstrate the versatility of the scheme, I show (1) run-time combination of toeholds and BM domains, (2) run-time recombination of toeholds and BM domains, which results in a novel operation ‘toehold switching’, and (3) the design of a simple conformational self-replicator.
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