IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50752-9.html
   My bibliography  Save this article

Atavistic strategy for the treatment of hyperuricemia via ionizable liposomal mRNA

Author

Listed:
  • Mengjie Zhang

    (Beijing Institute of Technology)

  • Abid Hussain

    (Beijing Institute of Technology)

  • Bo Hu

    (Beijing Institute of Technology)

  • Haiyin Yang

    (Beijing Institute of Technology)

  • Chunhui Li

    (Beijing Institute of Technology)

  • Shuai Guo

    (Beijing Institute of Technology)

  • Xiaofeng Han

    (Beijing Institute of Technology
    Rigerna Therapeutics Co. Ltd.)

  • Bei Li

    (University of Macau)

  • Yunlu Dai

    (University of Macau)

  • Yuhong Cao

    (National Center for Nanoscience and Technology, Chinese Academy of Sciences)

  • Hang Chi

    (Beijing Institute of Microbiology and Epidemiology)

  • Yuhua Weng

    (Beijing Institute of Technology)

  • Cheng-Feng Qin

    (Beijing Institute of Microbiology and Epidemiology)

  • Yuanyu Huang

    (Beijing Institute of Technology)

Abstract

Hyperuricemia is associated with an increased risk of gout, hypertension, diabetes, and cardiovascular diseases. Most mammals maintain normal serum uric acid (SUA) via urate oxidase (Uox), an enzyme that metabolizes poorly-soluble UA to highly-soluble allantoin. In contrast, Uox became a pseudogene in humans and apes over the long course of evolution. Here we demonstrate an atavistic strategy for treating hyperuricemia based on endogenous expression of Uox in hepatocytes mediated by mRNA (mUox) loaded with an ionizable lipid nanoparticle termed iLAND. mUox@iLAND allows effective transfection and protein expression in vitro. A single dose of mUox@iLAND lowers SUA levels for several weeks in two female murine models, including a novel long-lasting model, which is also confirmed by metabolomics analysis. Together with the excellent safety profiles observed in vivo, the proposed mRNA agent demonstrates substantial potential for hyperuricemia therapy and the prevention of associated conditions.

Suggested Citation

  • Mengjie Zhang & Abid Hussain & Bo Hu & Haiyin Yang & Chunhui Li & Shuai Guo & Xiaofeng Han & Bei Li & Yunlu Dai & Yuhong Cao & Hang Chi & Yuhua Weng & Cheng-Feng Qin & Yuanyu Huang, 2024. "Atavistic strategy for the treatment of hyperuricemia via ionizable liposomal mRNA," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50752-9
    DOI: 10.1038/s41467-024-50752-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50752-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-50752-9?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. Kathryn A. Whitehead & J. Robert Dorkin & Arturo J. Vegas & Philip H. Chang & Omid Veiseh & Jonathan Matthews & Owen S. Fenton & Yunlong Zhang & Karsten T. Olejnik & Volkan Yesilyurt & Delai Chen & Sc, 2014. "Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity," Nature Communications, Nature, vol. 5(1), pages 1-10, September.
    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. Yue Xu & Shihao Ma & Haotian Cui & Jingan Chen & Shufen Xu & Fanglin Gong & Alex Golubovic & Muye Zhou & Kevin Chang Wang & Andrew Varley & Rick Xing Ze Lu & Bo Wang & Bowen Li, 2024. "AGILE platform: a deep learning powered approach to accelerate LNP development for mRNA delivery," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Xuexiang Han & Junchao Xu & Ying Xu & Mohamad-Gabriel Alameh & Lulu Xue & Ningqiang Gong & Rakan El-Mayta & Rohan Palanki & Claude C. Warzecha & Gan Zhao & Andrew E. Vaughan & James M. Wilson & Drew W, 2024. "In situ combinatorial synthesis of degradable branched lipidoids for systemic delivery of mRNA therapeutics and gene editors," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Xuexiang Han & Hanwen Zhang & Kamila Butowska & Kelsey L. Swingle & Mohamad-Gabriel Alameh & Drew Weissman & Michael J. Mitchell, 2021. "An ionizable lipid toolbox for RNA delivery," Nature Communications, Nature, vol. 12(1), pages 1-6, December.
    4. Xuexiang Han & Ningqiang Gong & Lulu Xue & Margaret M. Billingsley & Rakan El-Mayta & Sarah J. Shepherd & Mohamad-Gabriel Alameh & Drew Weissman & Michael J. Mitchell, 2023. "Ligand-tethered lipid nanoparticles for targeted RNA delivery to treat liver fibrosis," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Roy Pattipeiluhu & Ye Zeng & Marco M.R.M. Hendrix & Ilja K. Voets & Alexander Kros & Thomas H. Sharp, 2024. "Liquid crystalline inverted lipid phases encapsulating siRNA enhance lipid nanoparticle mediated transfection," Nature Communications, Nature, vol. 15(1), pages 1-15, 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:15:y:2024:i:1:d:10.1038_s41467-024-50752-9. 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.