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Gene-encoding DNA origami for mammalian cell expression

Author

Listed:
  • Jessica A. Kretzmann

    (Technical University of Munich
    Technical University of Munich)

  • Anna Liedl

    (Technical University of Munich
    Technical University of Munich)

  • Alba Monferrer

    (Technical University of Munich
    Technical University of Munich)

  • Volodymyr Mykhailiuk

    (Technical University of Munich
    Technical University of Munich)

  • Samuel Beerkens

    (Technical University of Munich
    Technical University of Munich)

  • Hendrik Dietz

    (Technical University of Munich
    Technical University of Munich)

Abstract

DNA origami may enable more versatile gene delivery applications through its ability to create custom nanoscale objects with specific targeting, cell-invading, and intracellular effector functionalities. Toward this goal here we describe the expression of genes folded in DNA origami objects delivered to mammalian cells. Genes readily express from custom-sequence single-strand scaffolds folded within DNA origami objects, provided that the objects can denature in the cell. We demonstrate enhanced gene expression efficiency by including and tuning multiple functional sequences and structures, including virus-inspired inverted-terminal repeat-like (ITR) hairpin motifs upstream or flanking the expression cassette. We describe gene-encoding DNA origami bricks that assemble into multimeric objects to enable stoichiometrically controlled co-delivery and expression of multiple genes in the same cells. Our work provides a framework for exploiting DNA origami for gene delivery applications.

Suggested Citation

  • Jessica A. Kretzmann & Anna Liedl & Alba Monferrer & Volodymyr Mykhailiuk & Samuel Beerkens & Hendrik Dietz, 2023. "Gene-encoding DNA origami for mammalian cell expression," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36601-1
    DOI: 10.1038/s41467-023-36601-1
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    References listed on IDEAS

    as
    1. Nicholas S. McCarty & Alicia E. Graham & Lucie Studená & Rodrigo Ledesma-Amaro, 2020. "Multiplexed CRISPR technologies for gene editing and transcriptional regulation," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
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    3. Florian Praetorius & Benjamin Kick & Karl L. Behler & Maximilian N. Honemann & Dirk Weuster-Botz & Hendrik Dietz, 2017. "Biotechnological mass production of DNA origami," Nature, Nature, vol. 552(7683), pages 84-87, December.
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    Cited by:

    1. Linlin Tang & Zhijin Tian & Jin Cheng & Yijing Zhang & Yongxiu Song & Yan Liu & Jinghao Wang & Pengfei Zhang & Yonggang Ke & Friedrich C. Simmel & Jie Song, 2023. "Circular single-stranded DNA as switchable vector for gene expression in mammalian cells," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Zhijin Tian & Dandan Shao & Linlin Tang & Zhen Li & Qian Chen & Yongxiu Song & Tao Li & Friedrich C. Simmel & Jie Song, 2024. "Circular single-stranded DNA as a programmable vector for gene regulation in cell-free protein expression systems," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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