IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-42437-6.html
   My bibliography  Save this article

Circular single-stranded DNA as switchable vector for gene expression in mammalian cells

Author

Listed:
  • Linlin Tang

    (Shanghai Jiao Tong University)

  • Zhijin Tian

    (Chinese Academy of Sciences
    University of Science & Technology of China)

  • Jin Cheng

    (Shanghai Jiao Tong University)

  • Yijing Zhang

    (Chinese Academy of Sciences
    Tianjin University)

  • Yongxiu Song

    (Chinese Academy of Sciences)

  • Yan Liu

    (Shanghai Jiao Tong University)

  • Jinghao Wang

    (Chinese Academy of Sciences
    University of Science & Technology of China)

  • Pengfei Zhang

    (Chinese Academy of Sciences)

  • Yonggang Ke

    (Georgia Institute of Technology and Emory University)

  • Friedrich C. Simmel

    (Technische Universität München)

  • Jie Song

    (Shanghai Jiao Tong University
    Chinese Academy of Sciences)

Abstract

Synthetic gene networks in mammalian cells are currently limited to either protein-based transcription factors or RNA-based regulators. Here, we demonstrate a regulatory approach based on circular single-stranded DNA (Css DNA), which can be used as an efficient expression vector with switchable activity, enabling gene regulation in mammalian cells. The Css DNA is transformed into its double-stranded form via DNA replication and used as vectors encoding a variety of different proteins in a wide range of cell lines as well as in mice. The rich repository of DNA nanotechnology allows to use sort single-stranded DNA effectors to fold Css DNA into DNA nanostructures of different complexity, leading the gene expression to programmable inhibition and subsequently re-activation via toehold-mediated strand displacement. The regulatory strategy from Css DNA can thus expand the molecular toolbox for the realization of synthetic regulatory networks with potential applications in genetic diagnosis and gene therapy.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42437-6
    DOI: 10.1038/s41467-023-42437-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-42437-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-42437-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Simon Ausländer & David Ausländer & Marius Müller & Markus Wieland & Martin Fussenegger, 2012. "Programmable single-cell mammalian biocomputers," Nature, Nature, vol. 487(7405), pages 123-127, July.
    2. Yinan Zhang & Fei Wang & Jie Chao & Mo Xie & Huajie Liu & Muchen Pan & Enzo Kopperger & Xiaoguo Liu & Qian Li & Jiye Shi & Lihua Wang & Jun Hu & Lianhui Wang & Friedrich C. Simmel & Chunhai Fan, 2019. "DNA origami cryptography for secure communication," Nature Communications, Nature, vol. 10(1), pages 1-8, December.
    3. Alexander A. Green & Jongmin Kim & Duo Ma & Pamela A. Silver & James J. Collins & Peng Yin, 2017. "Complex cellular logic computation using ribocomputing devices," Nature, Nature, vol. 548(7665), pages 117-121, August.
    4. 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.
    5. Michael B. Elowitz & Stanislas Leibler, 2000. "A synthetic oscillatory network of transcriptional regulators," Nature, Nature, vol. 403(6767), pages 335-338, January.
    6. Timothy S. Gardner & Charles R. Cantor & James J. Collins, 2000. "Construction of a genetic toggle switch in Escherichia coli," Nature, Nature, vol. 403(6767), pages 339-342, January.
    7. Shawn M. Douglas & Hendrik Dietz & Tim Liedl & Björn Högberg & Franziska Graf & William M. Shih, 2009. "Self-assembly of DNA into nanoscale three-dimensional shapes," Nature, Nature, vol. 459(7245), pages 414-418, May.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Luna Rizik & Loai Danial & Mouna Habib & Ron Weiss & Ramez Daniel, 2022. "Synthetic neuromorphic computing in living cells," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Avraham E Mayo & Yaakov Setty & Seagull Shavit & Alon Zaslaver & Uri Alon, 2006. "Plasticity of the cis-Regulatory Input Function of a Gene," PLOS Biology, Public Library of Science, vol. 4(4), pages 1-1, March.
    3. Weiyue Ji & Handuo Shi & Haoqian Zhang & Rui Sun & Jingyi Xi & Dingqiao Wen & Jingchen Feng & Yiwei Chen & Xiao Qin & Yanrong Ma & Wenhan Luo & Linna Deng & Hanchi Lin & Ruofan Yu & Qi Ouyang, 2013. "A Formalized Design Process for Bacterial Consortia That Perform Logic Computing," PLOS ONE, Public Library of Science, vol. 8(2), pages 1-9, February.
    4. T. Ochiai & J. C. Nacher, 2007. "Stochastic analysis of autoregulatory gene expression dynamics," Mathematical and Computer Modelling of Dynamical Systems, Taylor & Francis Journals, vol. 14(4), pages 377-388, November.
    5. Thomas B. Kepler & Timothy C. Elston, 2001. "Stochasticity in Transcriptional Regulation: Origins, Consequences and Mathematical Representations," Working Papers 01-06-033, Santa Fe Institute.
    6. Luis Mier-y-Terán-Romero & Mary Silber & Vassily Hatzimanikatis, 2010. "The Origins of Time-Delay in Template Biopolymerization Processes," PLOS Computational Biology, Public Library of Science, vol. 6(4), pages 1-15, April.
    7. Tai-Yin Chiu & Hui-Ju K Chiang & Ruei-Yang Huang & Jie-Hong R Jiang & François Fages, 2015. "Synthesizing Configurable Biochemical Implementation of Linear Systems from Their Transfer Function Specifications," PLOS ONE, Public Library of Science, vol. 10(9), pages 1-27, September.
    8. Liu, Xian & Wang, Jinzhi & Huang, Lin, 2007. "Global synchronization for a class of dynamical complex networks," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 386(1), pages 543-556.
    9. Tobias May & Lee Eccleston & Sabrina Herrmann & Hansjörg Hauser & Jorge Goncalves & Dagmar Wirth, 2008. "Bimodal and Hysteretic Expression in Mammalian Cells from a Synthetic Gene Circuit," PLOS ONE, Public Library of Science, vol. 3(6), pages 1-7, June.
    10. Evgeni V Nikolaev & Eduardo D Sontag, 2016. "Quorum-Sensing Synchronization of Synthetic Toggle Switches: A Design Based on Monotone Dynamical Systems Theory," PLOS Computational Biology, Public Library of Science, vol. 12(4), pages 1-33, April.
    11. Zomorrodi, Ali R. & Maranas, Costas D., 2014. "Coarse-grained optimization-driven design and piecewise linear modeling of synthetic genetic circuits," European Journal of Operational Research, Elsevier, vol. 237(2), pages 665-676.
    12. Keun-Young Kim & Jin Wang, 2007. "Potential Energy Landscape and Robustness of a Gene Regulatory Network: Toggle Switch," PLOS Computational Biology, Public Library of Science, vol. 3(3), pages 1-13, March.
    13. Liu, Xian & Wang, Jinzhi & Huang, Lin, 2007. "Stabilization of a class of dynamical complex networks based on decentralized control," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 383(2), pages 733-744.
    14. Singh, Vijai & Chaudhary, Dharmendra Kumar & Mani, Indra & Dhar, Pawan Kumar, 2016. "Recent advances and challenges of the use of cyanobacteria towards the production of biofuels," Renewable and Sustainable Energy Reviews, Elsevier, vol. 60(C), pages 1-10.
    15. Samanthe M Lyons & Wenlong Xu & June Medford & Ashok Prasad, 2014. "Loads Bias Genetic and Signaling Switches in Synthetic and Natural Systems," PLOS Computational Biology, Public Library of Science, vol. 10(3), pages 1-16, March.
    16. Zhou, Peipei & Cai, Shuiming & Liu, Zengrong & Chen, Luonan & Wang, Ruiqi, 2013. "Coupling switches and oscillators as a means to shape cellular signals in biomolecular systems," Chaos, Solitons & Fractals, Elsevier, vol. 50(C), pages 115-126.
    17. Nasimul Noman & Taku Monjo & Pablo Moscato & Hitoshi Iba, 2015. "Evolving Robust Gene Regulatory Networks," PLOS ONE, Public Library of Science, vol. 10(1), pages 1-21, January.
    18. Ankit Gupta & Corentin Briat & Mustafa Khammash, 2014. "A Scalable Computational Framework for Establishing Long-Term Behavior of Stochastic Reaction Networks," PLOS Computational Biology, Public Library of Science, vol. 10(6), pages 1-16, June.
    19. Duncan Ingram & Guy-Bart Stan, 2023. "Modelling genetic stability in engineered cell populations," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    20. Lu, Wen & Zhang, Yuhao & Qian, Yu & Pandey, Vikas & Qu, Zhilin & Zhang, Zhaoyang, 2021. "Bursting and complex oscillatory patterns in a gene regulatory network model," Chaos, Solitons & Fractals, Elsevier, vol. 152(C).

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42437-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.