Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Journal Club
  • Published:

mRNA therapy

A zwitterionic twist

Nature Reviews Chemistry volume 8, page 721 (2024)Cite this article

Subjects

Messenger RNA (mRNA) garnered public attention during the coronavirus pandemic as a key component of mRNA vaccines. They have since been applied as therapeutics in numerous settings. In a typical system, mRNA — encoding the genetic building blocks of proteins — is encapsulated in vehicles such as lipid nanoparticles (LNPs) and delivered to individuals.

Recently, a team led by Shaoyi Jiang from Cornell University elucidated an intriguing twist that has the potential to enhance the PK profile of therapeutic proteins in mRNA-based PRT. Researchers designed an mRNA sequence that encodes a zwitterionic polypeptide twist, named EKP, that can be fused to the therapeutic protein of interest. EKP has an equal ratio of negatively charged glutamic acid (E) and positively charged lysine (K) with interspersed proline (P), creating a twisting configuration. The E and K components offer a non-fouling property, which prevents the body’s immune system from attacking the protein, thus improving its circulation time. The P component keeps the protein unstructured at high molecular weight, allowing the peptide sequence to elongate while retaining stability. Jiang and the team hypothesized that the in vivo translated EKP-fused protein from mRNA would have sustained PK profiles while maintaining bioactivity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

References

Original article

  • Luozhong, S. et al. A de novo strategy to improve pharmacokinetics of proteins from mRNA therapeutics via zwitterionic polypeptide fusion. J. Am. Chem. Soc. 146, 21245–21249 (2024)

    Article  PubMed  Google Scholar 

Related article

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Sihan Xiong

  2. Center for Stem Cell and Translational Immunotherapy, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Khalid Shah & Chuang Liu

  3. Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Khalid Shah & Chuang Liu

  4. Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA

    Khalid Shah

Authors
  1. Sihan Xiong
    View author publications

    Search author on:PubMed Google Scholar

  2. Khalid Shah
    View author publications

    Search author on:PubMed Google Scholar

  3. Chuang Liu
    View author publications

    Search author on:PubMed Google Scholar

Corresponding authors

Correspondence to Khalid Shah or Chuang Liu.

Ethics declarations

Competing interests

K.S. owns equity in and is a member of the Board of Directors of Amasa Therapeutics, a company developing stem cell-based therapies for cancer. K.S.’s interests were reviewed and are managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict-of-interest policies. The remaining authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xiong, S., Shah, K. & Liu, C. A zwitterionic twist. Nat Rev Chem 8, 721 (2024). https://doi.org/10.1038/s41570-024-00654-7

Download citation

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41570-024-00654-7

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer