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Title: Effective design principles for leakless strand displacement systems
Artificially designed molecular systems with programmable behaviors have become a valuable tool in chemistry, biology, material science, and medicine. Although information processing in biological regulatory pathways is remarkably robust to error, it remains a challenge to design molecular systems that are similarly robust. With functionality determined entirely by secondary structure of DNA, strand displacement has emerged as a uniquely versatile building block for cell-free biochemical networks. Here, we experimentally investigate a design principle to reduce undesired triggering in the absence of input (leak), a side reaction that critically reduces sensitivity and disrupts the behavior of strand displacement cascades. Inspired by error correction methods exploiting redundancy in electrical engineering, we ensure a higher-energy penalty to leak via logical redundancy. Our design strategy is, in principle, capable of reducing leak to arbitrarily low levels, and we experimentally test two levels of leak reduction for a core “translator” component that converts a signal of one sequence into that of another. We show that the leak was not measurable in the high-redundancy scheme, even for concentrations that are up to 100 times larger than typical. Beyond a single translator, we constructed a fast and low-leak translator cascade of nine strand displacement steps and a logic OR gate circuit consisting of 10 translators, showing that our design principle can be used to effectively reduce leak in more complex chemical systems.  more » « less
Award ID(s):
1718938 1213127 1317694 1652824
PAR ID:
10093584
Author(s) / Creator(s):
; ; ; ;
Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Volume:
115
Issue:
52
ISSN:
0027-8424
Page Range / eLocation ID:
E12182 to E12191
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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