IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-05096-6.html
   My bibliography  Save this article

Engineering circular RNA for potent and stable translation in eukaryotic cells

Author

Listed:
  • R. Alexander Wesselhoeft

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology)

  • Piotr S. Kowalski

    (Massachusetts Institute of Technology)

  • Daniel G. Anderson

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology)

Abstract

Messenger RNA (mRNA) has broad potential for application in biological systems. However, one fundamental limitation to its use is its relatively short half-life in biological systems. Here we develop exogenous circular RNA (circRNA) to extend the duration of protein expression from full-length RNA messages. First, we engineer a self-splicing intron to efficiently circularize a wide range of RNAs up to 5 kb in length in vitro by rationally designing ubiquitous accessory sequences that aid in splicing. We maximize translation of functional protein from these circRNAs in eukaryotic cells, and we find that engineered circRNA purified by high performance liquid chromatography displays exceptional protein production qualities in terms of both quantity of protein produced and stability of production. This study pioneers the use of exogenous circRNA for robust and stable protein expression in eukaryotic cells and demonstrates that circRNA is a promising alternative to linear mRNA.

Suggested Citation

  • R. Alexander Wesselhoeft & Piotr S. Kowalski & Daniel G. Anderson, 2018. "Engineering circular RNA for potent and stable translation in eukaryotic cells," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05096-6
    DOI: 10.1038/s41467-018-05096-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-05096-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-05096-6?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Hui Ning & Gan Liu & Lei Li & Qiang Liu & Huiya Huang & Zhen Xie, 2023. "Rational design of microRNA-responsive switch for programmable translational control in mammalian cells," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Chunwei Zheng & Bin Liu & Xiaolong Dong & Nicholas Gaston & Erik J. Sontheimer & Wen Xue, 2023. "Template-jumping prime editing enables large insertion and exon rewriting in vivo," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    3. Chan-I Su & Zih-Shiuan Chuang & Chi-Ting Shie & Hsin-I Wang & Yu-Ting Kao & Chia-Yi Yu, 2024. "A cis-acting ligase ribozyme generates circular RNA in vitro for ectopic protein functioning," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

    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:9:y:2018:i:1:d:10.1038_s41467-018-05096-6. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.