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Functionalizing DNA origami to investigate and interact with biological systems

Abstract

DNA origami has emerged as a powerful method to generate DNA nanostructures with dynamic properties and nanoscale control. These nanostructures enable complex biophysical studies and the fabrication of next-generation therapeutic devices. For these applications, DNA origami typically needs to be functionalized with bioactive ligands and biomacromolecular cargos. Here, we review methods developed to functionalize, purify and characterize DNA origami nanostructures. We identify remaining challenges such as limitations in functionalization efficiency and characterization. We then discuss where researchers can contribute to further advance the fabrication of functionalized DNA origami.

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Fig. 1: Functionalized DNA origami nanostructures interact with biological systems.
Fig. 2: A typical workflow for pre-assembly functionalization of DNA origami.
Fig. 3: A typical workflow for post-assembly functionalization of DNA origami.
Fig. 4: Methods to purify functionalized DNA origami nanostructures.
Fig. 5: Characterization techniques used to quantify the functionalization of DNA origami nanostructures.

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Acknowledgements

G.A.K., E.-C.W. and M.B. were supported by NIH R01-Al162307, NIH R21-EB026008-S1, ONR N00014-21-1-4013, ONR N00014-20-1-2084, NSF CCF-1956054, ARO ISN W911NF-13-D-0001 and ARO ICB Subaward KK1954. G.A.K. was additionally supported by the National Science Foundation under a Graduate Research Fellowship 2389237.

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Knappe, G.A., Wamhoff, EC. & Bathe, M. Functionalizing DNA origami to investigate and interact with biological systems. Nat Rev Mater 8, 123–138 (2023). https://doi.org/10.1038/s41578-022-00517-x

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