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  • Review Article
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Programming DNA machines to move

Abstract

DNA nanotechnology has rapidly evolved, leading to the development of dynamic nanoscale and microscale devices that mimic natural molecular machinery. This Review explores the latest advancements in DNA-based machines, motors and switches, emphasizing the need for clear definitions to distinguish between these often-interchanged terms. By analysing key performance metrics such as speed, force generation, efficiency and autonomy, we provide a framework for evaluating these devices against their biological counterparts, including motor proteins such as myosin and kinesin. We highlight innovative design strategies such as strand displacement, DNA origami and hybrid systems, which enhance the functionality of DNA-based constructs and bridge the gap between synthetic and natural systems. These advancements have promising applications in areas such as targeted drug delivery, biosensing and nanofabrication, although challenges in achieving the high performance and efficiency seen in biological systems remain. Through a synthesis of current research, this Review outlines the opportunities and challenges in the development of DNA-based nanoscale and microscale devices.

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Fig. 1: Classification of DNA machines.
Fig. 2: Synthetic rolling motors could have either a colloidal particle as a hub or a DNA origami scaffold.
Fig. 3: Survey of DNA-based motors as a function of size, speed and processivity.
Fig. 4: Design strategies to program DNA machines as molecular motors.
Fig. 5: Applications of DNA-based machines.

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Acknowledgements

The authors acknowledge support from Merck Future Insight Prize (to K.S.) and Joachim Herz Stiftung Global Impact Award (to S.P.).

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S.P. and L.Z. contributed equally to this work. S.P. and L.Z. researched data for the article and prepared the figures. S.P. and A.B. discussed content and outlined topics. W.D. helped perform research for the article and worked on Table 1. S.P., L.Z. and K.S. discussed the content and wrote the article.

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Correspondence to Khalid Salaita.

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Glossary

Burnt-bridge Brownian ratchet

(BBR). A molecular mechanism wherein motion is biased to a new foothold site by reducing the affinity to previously visited foothold sites through chemical or structural modifications.

DNA diffusive walkers

DNA strands or supramolecular constructs that move randomly on a 2D surface as an effect of thermal fluctuations.

DNA machines

Functional materials comprising DNA with the following features that mirror macroscopic machines: (1) consume chemical fuel to generate mechanical work, (2) processive and autonomous, (3) programmable and (4) responsive to inputs to perform functions such as cargo transport, sensing and drug release.

DNA motors

Molecular machines made of DNA that operate far from equilibrium by consuming energy to generate active motion.

DNA switches

Molecular constructs made of DNA that transition between two or more distinct states in response to an external input, such as light, pH change or force application.

Efficiency

The figure of merit used to evaluate the performance of a molecular motor based on its capability to convert the energy input into mechanical work.

Fuel

A molecule that is discarded or cleaved to allow a molecular motor to initiate a step by migrating to the successive attachment site.

Hub

An inert body used by a molecular motor to coordinate the movement of multiple legs.

Polyvalency

Also known as multivalency; the state or condition of a molecular motor that has multiple attachment contacts with its track at any given time.

Processivity

The ability of a molecular motor to undertake multiple steps without dissociating from its track.

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Piranej, S., Zhang, L., Bazrafshan, A. et al. Programming DNA machines to move. Nat Rev Chem (2026). https://doi.org/10.1038/s41570-025-00791-7

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