Folding of mRNA-DNA Origami for Controlled Translation and Viral Vector Packaging

Iris Seitz; Sharon Saarinen; Julia Wierzchowiecka; Esa-Pekka Kumpula; Boxuan Shen; Jeroen J.L.M. Cornelissen; Veikko Linko; Juha T. Huiskonen; Mauri A. Kostiainen

doi:10.1002/adma.202417642

Folding of mRNA-DNA Origami for Controlled Translation and Viral Vector Packaging

Iris Seitz, Sharon Saarinen, Julia Wierzchowiecka, Esa-Pekka Kumpula, Boxuan Shen, Jeroen J.L.M. Cornelissen, Veikko Linko, Juha T. Huiskonen, Mauri A. Kostiainen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Scientific › peer-review

5 Citations (Scopus)

14 Downloads (Pure)

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, comprehensive studies on the requirements for efficient folding of mRNA into distinct mRNA-DNA structures while preserving its translation functionality remain elusive. Here, the impact of design parameters on the folding of protein-encoding mRNA into mRNA-DNA origami structures is systematically investigated and the importance of the availability of ribosome-binding sequences on the translation efficiency is demonstrated. Furthermore, these hybrid structures are encapsulated inside virus capsids resulting in protecting them against nuclease degradation and also in enhancement of their cellular uptake. This multicomponent system therefore showcases a modular and versatile nanocarrier. The work provides valuable insight into the design of mRNA-DNA origami structures contributing to the development of mRNA-based gene delivery platforms.

Original language	English
Article number	2417642
Journal	Advanced Materials
Volume	37
Issue number	15
Early online date	27 Feb 2025
DOIs	https://doi.org/10.1002/adma.202417642
Publication status	Published - 16 Apr 2025
MoE publication type	A1 Journal article-refereed

Funding

The authors acknowledge financial support from the European Research Council (ERC) and ERA Chair MATTER under European Union's Horizon 2020 research and innovation programme (grant agreement no. 101002258 and 856705), Academy of Finland (project no. 341908), Emil Aaltonen Foundation and Jane and Aatos Erkko Foundation. The authors thank Ahmed Shaukat for his assistance with cell culturing. This work was carried out under the Academy of Finland Centers of Excellence Program (2022-2029) in Life-Inspired Hybrid Materials (LIBER), project number (346110). The authors acknowledge the provision of facilities and technical support by Aalto University Bioeconomy Facilities, OtaNanoNanomicroscopy Center (Aalto-NMC) and Micronova Nanofabrication Center. We thank Kiran Ahmad and Tuomas Niemi-Aro (University of Helsinki) for technical assistance in cryoEM. The facilities and expertise of the HiLIFE CryoEM unit at the University of Helsinki, a member of Instruct-ERIC Centre Finland, FINStruct, and Biocenter Finland are gratefully acknowledged. For SciLifeLab (Stockholm), we thank Karin Walldén for data collection support.

Keywords

cellular delivery
mRNA translation
mRNA-DNA origami
virus capsid proteins

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/adma.202417642Licence: CC BY

Folding of mRNA‐DNA Origami for Controlled Translation and Viral Vector PackagingFinal published version, 9.11 MBLicence: CC BY

Cite this

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title = "Folding of mRNA-DNA Origami for Controlled Translation and Viral Vector Packaging",

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, comprehensive studies on the requirements for efficient folding of mRNA into distinct mRNA-DNA structures while preserving its translation functionality remain elusive. Here, the impact of design parameters on the folding of protein-encoding mRNA into mRNA-DNA origami structures is systematically investigated and the importance of the availability of ribosome-binding sequences on the translation efficiency is demonstrated. Furthermore, these hybrid structures are encapsulated inside virus capsids resulting in protecting them against nuclease degradation and also in enhancement of their cellular uptake. This multicomponent system therefore showcases a modular and versatile nanocarrier. The work provides valuable insight into the design of mRNA-DNA origami structures contributing to the development of mRNA-based gene delivery platforms.",

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N2 - 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, comprehensive studies on the requirements for efficient folding of mRNA into distinct mRNA-DNA structures while preserving its translation functionality remain elusive. Here, the impact of design parameters on the folding of protein-encoding mRNA into mRNA-DNA origami structures is systematically investigated and the importance of the availability of ribosome-binding sequences on the translation efficiency is demonstrated. Furthermore, these hybrid structures are encapsulated inside virus capsids resulting in protecting them against nuclease degradation and also in enhancement of their cellular uptake. This multicomponent system therefore showcases a modular and versatile nanocarrier. The work provides valuable insight into the design of mRNA-DNA origami structures contributing to the development of mRNA-based gene delivery platforms.

AB - 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, comprehensive studies on the requirements for efficient folding of mRNA into distinct mRNA-DNA structures while preserving its translation functionality remain elusive. Here, the impact of design parameters on the folding of protein-encoding mRNA into mRNA-DNA origami structures is systematically investigated and the importance of the availability of ribosome-binding sequences on the translation efficiency is demonstrated. Furthermore, these hybrid structures are encapsulated inside virus capsids resulting in protecting them against nuclease degradation and also in enhancement of their cellular uptake. This multicomponent system therefore showcases a modular and versatile nanocarrier. The work provides valuable insight into the design of mRNA-DNA origami structures contributing to the development of mRNA-based gene delivery platforms.

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Folding of mRNA-DNA Origami for Controlled Translation and Viral Vector Packaging

Abstract

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

ProCrystal (ERC): Multicomponent Protein Cage Co-Crystals

SiDNAno/Shen: Silica-DNA Hybrid Nanostructures as Next Generation Self-Assembling Nanomaterials

Bioeconomy Research Infrastructure

OtaNano

OtaNano - Nanofab

Cite this

Folding of mRNA-DNA Origami for Controlled Translation and Viral Vector Packaging

Abstract

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

ProCrystal (ERC): Multicomponent Protein Cage Co-Crystals

SiDNAno/Shen: Silica-DNA Hybrid Nanostructures as Next Generation Self-Assembling Nanomaterials

Equipment

Bioeconomy Research Infrastructure

OtaNano

OtaNano - Nanofab

Cite this