Nanodevices for the Efficient Codelivery of CRISPR-Cas9 Editing Machinery and an Entrapped Cargo: A Proposal for Dual Anti-Inflammatory Therapy.

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Garcia-Fernandez, Alba
  • Vivo-Llorca, Gema
  • Sancho, Monica
  • García-Jareño AB
  • Ramirez-Jimenez, Laura
  • Barber-Cano, Eloisa
  • Murguía JR
  • Orzaez, Mar

Grupos

Abstract

In this article, we report one of the few examples of nanoparticles capable of simultaneously delivering CRISPR-Cas9 gene-editing machinery and releasing drugs for one-shot treatments. Considering the complexity of inflammation in diseases, the synergistic effect of nanoparticles for gene-editing/drug therapy is evaluated in an in vitro inflammatory model as proof of concept. Mesoporous silica nanoparticles (MSNs), able to deliver the CRISPR/Cas9 machinery to edit gasdermin D (GSDMD), a key protein involved in inflammatory cell death, and the anti-inflammatory drug VX-765 ((CRISPR)-C-GSDMD45-VX-MSNs), were prepared. Nanoparticles allow high cargo loading and CRISPR-Cas9 plasmid protection and, thus, achieve the controlled codelivery of CRISPR-Cas9 and the drug in cells. Nanoparticles exhibit GSDMD gene editing by downregulating inflammatory cell death and achieving a combined effect on decreasing the inflammatory response by the codelivery of VX-765. Taken together, our results show the potential of MSNs as a versatile platform by allowing multiple combinations for gene editing and drug therapy to prepare advanced nanodevices to meet possible biomedical needs.

Datos de la publicación

ISSN/ISSNe:
1999-4923, 1999-4923

Pharmaceutics  Multidisciplinary Digital Publishing Institute (MDPI)

Tipo:
Article
Páginas:
-
PubMed:
35890389
Factor de Impacto:
0,922 SCImago
Cuartil:
Q1 SCImago

Citas Recibidas en Web of Science: 11

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Keywords

  • mesoporous silica nanoparticles; CRISPR-Cas9; gene editing; inflammation; drug delivery

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