IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33157-4.html
   My bibliography  Save this article

Payload distribution and capacity of mRNA lipid nanoparticles

Author

Listed:
  • Sixuan Li

    (Johns Hopkins University)

  • Yizong Hu

    (Johns Hopkins University
    Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Andrew Li

    (Johns Hopkins University School of Medicine)

  • Jinghan Lin

    (Johns Hopkins University
    Johns Hopkins University School of Medicine)

  • Kuangwen Hsieh

    (Johns Hopkins University)

  • Zachary Schneiderman

    (Johns Hopkins University
    Johns Hopkins University)

  • Pengfei Zhang

    (Johns Hopkins University School of Medicine)

  • Yining Zhu

    (Johns Hopkins University
    Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Chenhu Qiu

    (Johns Hopkins University
    Johns Hopkins University)

  • Efrosini Kokkoli

    (Johns Hopkins University
    Johns Hopkins University)

  • Tza-Huei Wang

    (Johns Hopkins University
    Johns Hopkins University
    Johns Hopkins University School of Medicine)

  • Hai-Quan Mao

    (Johns Hopkins University
    Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine
    Johns Hopkins University)

Abstract

Lipid nanoparticles (LNPs) are effective vehicles to deliver mRNA vaccines and therapeutics. It has been challenging to assess mRNA packaging characteristics in LNPs, including payload distribution and capacity, which are critical to understanding structure-property-function relationships for further carrier development. Here, we report a method based on the multi-laser cylindrical illumination confocal spectroscopy (CICS) technique to examine mRNA and lipid contents in LNP formulations at the single-nanoparticle level. By differentiating unencapsulated mRNAs, empty LNPs and mRNA-loaded LNPs via coincidence analysis of fluorescent tags on different LNP components, and quantitatively resolving single-mRNA fluorescence, we reveal that a commonly referenced benchmark formulation using DLin-MC3 as the ionizable lipid contains mostly 2 mRNAs per loaded LNP with a presence of 40%–80% empty LNPs depending on the assembly conditions. Systematic analysis of different formulations with control variables reveals a kinetically controlled assembly mechanism that governs the payload distribution and capacity in LNPs. These results form the foundation for a holistic understanding of the molecular assembly of mRNA LNPs.

Suggested Citation

  • Sixuan Li & Yizong Hu & Andrew Li & Jinghan Lin & Kuangwen Hsieh & Zachary Schneiderman & Pengfei Zhang & Yining Zhu & Chenhu Qiu & Efrosini Kokkoli & Tza-Huei Wang & Hai-Quan Mao, 2022. "Payload distribution and capacity of mRNA lipid nanoparticles," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33157-4
    DOI: 10.1038/s41467-022-33157-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33157-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-33157-4?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. 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.
    2. Yu Zhao & Zhongfeng Ye & Donghui Song & Douglas Wich & Shuliang Gao & Jennifer Khirallah & Qiaobing Xu, 2023. "Nanomechanical action opens endo-lysosomal compartments," Nature Communications, Nature, vol. 14(1), pages 1-11, 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:13:y:2022:i:1:d:10.1038_s41467-022-33157-4. 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.