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bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.25.609594
preprint
1
Article
AI-based Prediction of Protein Corona Composition on DNA Nanostructures
Huzar Jared http://orcid.org/0000-0001-5085-0554

Coreas Roxana http://orcid.org/0000-0001-6057-4717

Landry Markita P. http://orcid.org/0000-0002-5832-8522

Tikhomirov Grigory http://orcid.org/0000-0001-6061-3843

26 8 2024
2024.08.25.609594https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.25.609594
nihpp-2024.08.25.609594.pdf
Abstract

DNA nanotechnology has emerged as a powerful approach to engineering biophysical tools, therapeutics, and diagnostics because it enables the construction of designer nanoscale structures with high programmability. Based on DNA base pairing rules, nanostructure size, shape, surface functionality, and structural reconfiguration can be programmed with a degree of spatial, temporal, and energetic precision that is difficult to achieve with other methods. However, the properties and structure of DNA constructs are greatly altered in vivo due to spontaneous protein adsorption from biofluids. These adsorbed proteins, referred to as the protein corona, remain challenging to control or predict, and subsequently, their functionality and fate in vivo are difficult to engineer. To address these challenges, we prepared a library of diverse DNA nanostructures and investigated the relationship between their design features and the composition of their protein corona. We identified protein characteristics important for their adsorption to DNA nanostructures and developed a machine-learning model that predicts which proteins will be enriched on a DNA nanostructure based on the DNA structures’ design features and protein properties. Our work will help to understand and program the function of DNA nanostructures in vivo for biophysical and biomedical applications.
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