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bioRxiv · 10.1101/2024.05.29.596417

Folding of mRNA-DNA origami for controlled translation and viral vector packaging

Seitz, I.·Saarinen, S.·Wierzchowiecka, J.·Cornelissen, J. J. L. M.·Linko, V.·Kostiainen, M. A.
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Abstract

mRNA is an important molecule in vaccine development and treatment of genetic disorders. Its capability to hybridize with DNA oligonucleotides in a programmable manner facilitates the formation of RNA-DNA origami structures, which can possess a well-defined morphology and serve as rigid supports for mRNA delivery. However, to date, compre- hensive studies on the requirements for efficient folding of mRNA into distinct mRNA-DNA structures while preserving its translation func- tionality remain elusive. Here, we systematically investigate the impact of design parameters on the folding of protein-encoding mRNA into mRNA-DNA origami structures and demonstrate the importance of the availability of ribosome-binding sequences on the translation effi- ciency. Furthermore, these hybrid structures can be encapsulated inside virus capsids for protecting them against nuclease degradation and also for enhancing their cellular uptake. This multicomponent system therefore showcases a modular and versatile nanocarrier. Our work pro- vides valuable insight into the design of mRNA-DNA origami structures contributing to the development of mRNA-based gene delivery platforms.

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Seitz, I., Saarinen, S., Wierzchowiecka, J., Cornelissen, J. J. L. M., Linko, V., Kostiainen, M. A.. 2024-06-02. Folding of mRNA-DNA origami for controlled translation and viral vector packaging. https://doi.org/10.1101/2024.05.29.596417

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