Scientific Reports (Apr 2023)

Lipid-coated mesoporous silica nanoparticles for anti-viral applications via delivery of CRISPR-Cas9 ribonucleoproteins

  • Annette E. LaBauve,
  • Edwin A. Saada,
  • Iris K. A. Jones,
  • Richard Mosesso,
  • Achraf Noureddine,
  • Jessica Techel,
  • Andrew Gomez,
  • Nicole Collette,
  • Michael B. Sherman,
  • Rita E. Serda,
  • Kimberly S. Butler,
  • C. Jeffery Brinker,
  • Joseph S. Schoeniger,
  • Darryl Sasaki,
  • Oscar A. Negrete

DOI
https://doi.org/10.1038/s41598-023-33092-4
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 13

Abstract

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Abstract Emerging and re-emerging viral pathogens present a unique challenge for anti-viral therapeutic development. Anti-viral approaches with high flexibility and rapid production times are essential for combating these high-pandemic risk viruses. CRISPR-Cas technologies have been extensively repurposed to treat a variety of diseases, with recent work expanding into potential applications against viral infections. However, delivery still presents a major challenge for these technologies. Lipid-coated mesoporous silica nanoparticles (LCMSNs) offer an attractive delivery vehicle for a variety of cargos due to their high biocompatibility, tractable synthesis, and amenability to chemical functionalization. Here, we report the use of LCMSNs to deliver CRISPR-Cas9 ribonucleoproteins (RNPs) that target the Niemann–Pick disease type C1 gene, an essential host factor required for entry of the high-pandemic risk pathogen Ebola virus, demonstrating an efficient reduction in viral infection. We further highlight successful in vivo delivery of the RNP-LCMSN platform to the mouse liver via systemic administration.