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

Autores de CIPF

• Alba Garcia Fernandez

  Autor

• 

  Mónica Sancho Medina

  Autor

• Alicia Bel García Jareño

  Autor

• Laura Ramirez Jimenez

  Autor

• 

  Maria Mar Orzáez Calatayud

  Autor

• Félix Sancenón Galarza

  Autor

• Ramón Martínez Mañez

  Autor

Participantes ajenos a CIPF

• Vivo-Llorca, G
• Barber-Cano, E
• Murguia, JR

Grupos de Investigación

• Laboratorio de Terapias Dirigidas en Cáncer e Inflamación

  

  Jefe/a de Grupo

  Maria Mar Orzáez Calatayud

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.

Keywords

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