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Structuring lipid nanoparticles, DNA, and protein corona into stealth bionanoarchitectures for in vivo gene delivery

Author

Listed:
  • Serena Renzi

    (Sapienza University of Rome)

  • Luca Digiacomo

    (Sapienza University of Rome)

  • Daniela Pozzi

    (Sapienza University of Rome)

  • Erica Quagliarini

    (Sapienza University of Rome)

  • Elisabetta Vulpis

    (Sapienza University of Rome)

  • Maria Valeria Giuli

    (Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti)

  • Angelica Mancusi

    (Sapienza University of Rome)

  • Bianca Natiello

    (Sapienza University of Rome)

  • Maria Gemma Pignataro

    (Sapienza University of Rome)

  • Gianluca Canettieri

    (Sapienza University of Rome)

  • Laura Magno

    (Sapienza University of Rome)

  • Luca Pesce

    (Scuola Normale Superiore)

  • Valentina Lorenzi

    (Scuola Normale Superiore)

  • Samuele Ghignoli

    (Scuola Normale Superiore)

  • Luisa Loconte

    (Sapienza University of Rome)

  • Carmela Maria Montone

    (Sapienza University of Rome)

  • Anna Laura Capriotti

    (Sapienza University of Rome)

  • Aldo Laganà

    (Sapienza University of Rome)

  • Carmine Nicoletti

    (Sapienza University of Rome)

  • Heinz Amenitsch

    (Graz University of Technology)

  • Marco Rossi

    (Sapienza University of Rome)

  • Francesco Mura

    (Sapienza University of Rome)

  • Giacomo Parisi

    (Sapienza University of Rome)

  • Francesco Cardarelli

    (Scuola Normale Superiore)

  • Alessandra Zingoni

    (Sapienza University of Rome)

  • Saula Checquolo

    (Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti)

  • Giulio Caracciolo

    (Sapienza University of Rome)

Abstract

Lipid nanoparticles (LNPs) play a crucial role in addressing genetic disorders, and cancer, and combating pandemics such as COVID-19 and its variants. Yet, the ability of LNPs to effectively encapsulate large-size DNA molecules remains elusive. This is a significant limitation, as the successful delivery of large-size DNA holds immense potential for gene therapy. To address this gap, the present study focuses on the design of PEGylated LNPs, incorporating large-sized DNA, departing from traditional RNA and ionizable lipids. The resultant LNPs demonstrate a unique particle morphology. These particles were further engineered with a DNA coating and plasma proteins. This multicomponent bionanoconstruct exhibits enhanced transfection efficiency and safety in controlled laboratory settings and improved immune system evasion in in vivo tests. These findings provide valuable insights for the design and development of bionanoarchitectures for large-size DNA delivery, opening new avenues for transformative gene therapies.

Suggested Citation

  • Serena Renzi & Luca Digiacomo & Daniela Pozzi & Erica Quagliarini & Elisabetta Vulpis & Maria Valeria Giuli & Angelica Mancusi & Bianca Natiello & Maria Gemma Pignataro & Gianluca Canettieri & Laura M, 2024. "Structuring lipid nanoparticles, DNA, and protein corona into stealth bionanoarchitectures for in vivo gene delivery," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53569-8
    DOI: 10.1038/s41467-024-53569-8
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    References listed on IDEAS

    as
    1. Yining Zhu & Ruochen Shen & Ivan Vuong & Rebekah A. Reynolds & Melanie J. Shears & Zhi-Cheng Yao & Yizong Hu & Won June Cho & Jiayuan Kong & Sashank K. Reddy & Sean C. Murphy & Hai-Quan Mao, 2022. "Multi-step screening of DNA/lipid nanoparticles and co-delivery with siRNA to enhance and prolong gene expression," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Rossitza N. Irobalieva & Jonathan M. Fogg & Daniel J. Catanese & Thana Sutthibutpong & Muyuan Chen & Anna K. Barker & Steven J. Ludtke & Sarah A. Harris & Michael F. Schmid & Wah Chiu & Lynn Zechiedri, 2015. "Erratum: Structural diversity of supercoiled DNA," Nature Communications, Nature, vol. 6(1), pages 1-1, December.
    3. Rossitza N. Irobalieva & Jonathan M. Fogg & Daniel J. Catanese & Thana Sutthibutpong & Muyuan Chen & Anna K. Barker & Steven J. Ludtke & Sarah A. Harris & Michael F. Schmid & Wah Chiu & Lynn Zechiedri, 2015. "Structural diversity of supercoiled DNA," Nature Communications, Nature, vol. 6(1), pages 1-11, December.
    4. Lays Cordeiro Guimaraes & Pedro Augusto Carvalho Costa & Sérgio Ricardo Aluotto Scalzo Júnior & Heloísa Athaydes Seabra Ferreira & Ana Carolina Soares Braga & Leonardo Camilo Oliveira & Maria Marta Fi, 2024. "Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    5. Francesca Giulimondi & Luca Digiacomo & Daniela Pozzi & Sara Palchetti & Elisabetta Vulpis & Anna Laura Capriotti & Riccardo Zenezini Chiozzi & Aldo Laganà & Heinz Amenitsch & Laura Masuelli & Giovann, 2019. "Interplay of protein corona and immune cells controls blood residency of liposomes," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
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