Engineering
            <scp>DNA</scp>
            Switches for
            <scp>DNA</scp>
            Computing Applications

Lauzon, Dominic; Zhu, Guichi; Vallée‐Bélisle, Alexis

doi:10.1002/9783527825424.ch7

Cited by 2 publications

(2 citation statements)

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“…Furthermore, multivalent activators provide a way to rationally tune the half-life of the “ON-state” of the switch ( k off ) while not affecting its activation rate ( k on ), which can still be optimized through an allosteric activation mechanism if needed. Ultimately, the ability to rationally control the properties of molecular switches through the formation of a multivalent assembly can find many applications in DNA-based nanotechnologies to improve the binding efficiency of DNA switches, to modulate the drug release properties of DNA cargo, to increase the residence time of activated switches, or to program DNA-based computation. , …”

Section: Discussionmentioning

confidence: 99%

“…Ultimately, the ability to rationally control the properties of molecular switches through the formation of a multivalent assembly can find many applications in DNA-based nanotechnologies to improve the binding efficiency of DNA switches, to modulate the drug release properties of DNA cargo, to increase the residence time of activated switches, or to program DNA-based computation. 50,51 More specifically, we also demonstrated how the multivalent activation strategy can be used to program and optimize other nanosystems. For example, by adding a multivalent activator mechanism to a previously reported antibody switch, 39 we demonstrated how this switch could be further programed to detect antibodies over the desired, optimal dynamic range.…”

Section: ■ Discussionmentioning

confidence: 99%

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Programing Chemical Communication: Allostery vs Multivalent Mechanism

Lauzon

Vallée‐Bélisle

2023

J. Am. Chem. Soc.

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The emergence of life has relied on chemical communication and the ability to integrate multiple chemical inputs into a specific output. Two mechanisms are typically employed by nature to do so: allostery and multivalent activation. Although a better understanding of allostery has recently provided a variety of strategies to optimize the binding affinity, sensitivity, and specificity of molecular switches, mechanisms relying on multivalent activation remain poorly understood. As a proof of concept to compare the thermodynamic basis and design principles of both mechanisms, we have engineered a highly programmable DNA-based switch that can be triggered by either a multivalent or an allosteric DNA activator. By precisely designing the binding interface of the multivalent activator, we show that the affinity, dynamic range, and activated half-life of the molecular switch can be programed with even more versatility than when using an allosteric activator. The simplicity by which the activation properties of molecular switches can be rationally tuned using multivalent assembly suggests that it may find many applications in biosensing, drug delivery, synthetic biology, and molecular computation fields, where precise control over the transduction of binding events into a specific output is key.

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Section: Discussionmentioning

confidence: 99%