Leak-resilient enzyme-free nucleic acid dynamical systems through shadow cancellation

DNA strand displacement (DSD) emerged as a prominent reaction motif for
engineering nucleic acid-based computational devices with programmable
behaviors. However, strand displacement circuits are susceptible to
background noise that disrupts the circuit behavior, commonly known as
leaks. The side effects of leaks are particularly severe in circuits with
complex dynamical elements (e.g., feedback loops), as their leaks amplify
nonlinearly, disrupting the circuit function. Shadow cancellation is a
dynamic leak-elimination strategy originally proposed to control the leak
growth in such circuits. However, the kinetic restrictions of the proposed
method introduce a significant design overhead, making it less accessible.
In this work, we use domain-level DSD simulations to examine the
method's capabilities, the inner workings of its components, and,
most importantly, robustness to practical deviations in its design
requirements. First, we show that the method could stabilize the dynamics
of several leak-affected catalytic and autocatalytic dynamical systems of
practical importance. Then, through several probing experiments, we show
that its design restrictions could be significantly relaxed without
impacting the circuit function through simple adjustments to the circuit
parameters. Finally, we discuss several ideas to tackle the practical
challenges in applying the method to arbitrary DSD circuits, paving the
way for future experimental work.