Nanodevices for the Efficient Codelivery of CRISPR-Cas9 Editing Machinery and an Entrapped Cargo: A Proposal for Dual Anti-Inflammatory Therapy
Por:
A. GARCIA-FERNANDEZ, G. VIVO-LLORCA, M. SANCHO, A. GARCIA-JARENO, L. RAMIREZ-JIMENEZ, E. BARBER-CANO, J. MURGUIA, M. ORZAEZ, F. SANCENON and R. MARTINEZ-MANEZ
Publicada:
1 jul 2022
Resumen:
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.
Filiaciones:
:
Univ Politecn Valencia, Univ Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarr, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid 28029, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermeda, Valencia 46012, Spain
G. VIVO-LLORCA:
Univ Politecn Valencia, Univ Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarr, Valencia 46022, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermeda, Valencia 46012, Spain
:
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermeda, Valencia 46012, Spain
Ctr Invest Principe Felipe, Valencia 46012, Spain
:
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermeda, Valencia 46012, Spain
Ctr Invest Principe Felipe, Valencia 46012, Spain
:
Ctr Invest Principe Felipe, Valencia 46012, Spain
E. BARBER-CANO:
Ctr Invest Principe Felipe, Valencia 46012, Spain
J. MURGUIA:
Univ Politecn Valencia, Univ Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarr, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid 28029, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermeda, Valencia 46012, Spain
:
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermeda, Valencia 46012, Spain
Ctr Invest Principe Felipe, Valencia 46012, Spain
:
Univ Politecn Valencia, Univ Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarr, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid 28029, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermeda, Valencia 46012, Spain
UPV IIS La Fe, Unidad Mixta Invest Nanomed & Sensores, Valencia 46026, Spain
:
Univ Politecn Valencia, Univ Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarr, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid 28029, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermeda, Valencia 46012, Spain
UPV IIS La Fe, Unidad Mixta Invest Nanomed & Sensores, Valencia 46026, Spain
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