IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v615y2023i7953d10.1038_s41586-023-05824-z.html
   My bibliography  Save this article

A swapped genetic code prevents viral infections and gene transfer

Author

Listed:
  • Akos Nyerges

    (Harvard Medical School)

  • Svenja Vinke

    (Harvard Medical School)

  • Regan Flynn

    (Harvard Medical School)

  • Siân V. Owen

    (Harvard Medical School)

  • Eleanor A. Rand

    (Harvard Medical School)

  • Bogdan Budnik

    (Harvard University)

  • Eric Keen

    (Washington University School of Medicine in St. Louis
    Washington University School of Medicine in St. Louis)

  • Kamesh Narasimhan

    (Harvard Medical School)

  • Jorge A. Marchand

    (Harvard Medical School
    University of Washington)

  • Maximilien Baas-Thomas

    (Harvard Medical School)

  • Min Liu

    (GenScript USA Inc.)

  • Kangming Chen

    (GenScript USA Inc.)

  • Anush Chiappino-Pepe

    (Harvard Medical School)

  • Fangxiang Hu

    (GenScript USA Inc.)

  • Michael Baym

    (Harvard Medical School)

  • George M. Church

    (Harvard Medical School
    Harvard University)

Abstract

Engineering the genetic code of an organism has been proposed to provide a firewall from natural ecosystems by preventing viral infections and gene transfer1–6. However, numerous viruses and mobile genetic elements encode parts of the translational apparatus7–9, potentially rendering a genetic-code-based firewall ineffective. Here we show that such mobile transfer RNAs (tRNAs) enable gene transfer and allow viral replication in Escherichia coli despite the genome-wide removal of 3 of the 64 codons and the previously essential cognate tRNA and release factor genes. We then establish a genetic firewall by discovering viral tRNAs that provide exceptionally efficient codon reassignment allowing us to develop cells bearing an amino acid-swapped genetic code that reassigns two of the six serine codons to leucine during translation. This amino acid-swapped genetic code renders cells resistant to viral infections by mistranslating viral proteomes and prevents the escape of synthetic genetic information by engineered reliance on serine codons to produce leucine-requiring proteins. As these cells may have a selective advantage over wild organisms due to virus resistance, we also repurpose a third codon to biocontain this virus-resistant host through dependence on an amino acid not found in nature10. Our results may provide the basis for a general strategy to make any organism safely resistant to all natural viruses and prevent genetic information flow into and out of genetically modified organisms.

Suggested Citation

  • Akos Nyerges & Svenja Vinke & Regan Flynn & Siân V. Owen & Eleanor A. Rand & Bogdan Budnik & Eric Keen & Kamesh Narasimhan & Jorge A. Marchand & Maximilien Baas-Thomas & Min Liu & Kangming Chen & Anus, 2023. "A swapped genetic code prevents viral infections and gene transfer," Nature, Nature, vol. 615(7953), pages 720-727, March.
    • Handle: RePEc:nat:nature:v:615:y:2023:i:7953:d:10.1038_s41586-023-05824-z
    DOI: 10.1038/s41586-023-05824-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-023-05824-z
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41586-023-05824-z?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

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


    Cited by:

    1. Tiantian Chang & Weichao Ding & Shirui Yan & Yun Wang & Haoling Zhang & Yu Zhang & Zhi Ping & Huiming Zhang & Yijian Huang & Jiahui Zhang & Dan Wang & Wenwei Zhang & Xun Xu & Yue Shen & Xian Fu, 2023. "A robust yeast biocontainment system with two-layered regulation switch dependent on unnatural amino acid," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Kasimir Kienbeck & Lukas Malfertheiner & Susann Zelger-Paulus & Silke Johannsen & Christian Mering & Roland K. O. Sigel, 2024. "Identification of HDV-like theta ribozymes involved in tRNA-based recoding of gut bacteriophages," 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:nature:v:615:y:2023:i:7953:d:10.1038_s41586-023-05824-z. 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.