Journal Article Epublish 19 citations
PubMed: 35890389 DOI: 10.3390/pharmaceutics14071495
Nanodevices for the Efficient Codelivery of CRISPR-Cas9 Editing Machinery and an Entrapped Cargo: A Proposal for Dual Anti-Inflammatory Therapy.
Pharmaceutics 14(7)
Authors: Alba García-Fernández, Gema Vivo-Llorca, Mónica Sancho, Alicia Belén García-Jareño, Laura Ramírez-Jiménez, Eloísa Barber-Cano, José Ramón Murguía, Mar Orzáez, Félix Sancenón, Ramón Martínez-Máñez
Affiliations
- Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, 46022 Valencia, Spain.
- CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain.
- Unidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina, Centro de Investigación Príncipe Felipe, Universitat Politècnica de València, 46012 Valencia, Spain.
- Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain.
- Unidad Mixta de Investigación en Nanomedicina y Sensores, UPV-IIS La Fe, 46026 Valencia, Spain.
- Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, 46022 Valencia, Spain. CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain. Unidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina, Centro de Investigación Príncipe Felipe, Universitat Politècnica de València, 46012 Valencia, Spain. Unidad Mixta de Investigación en Nanomedicina y Sensores, UPV-IIS La Fe, 46026 Valencia, Spain.
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-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.
MeSH
Drug Therapy, Clustered Regularly Interspaced Short Palindromic Repeats, Pharmaceutical Preparations, Cells, Therapeutics, Cell Death, Nanoparticles, Genes
Cited by
- Advances in CRISPR-Cas9 for the Baculovirus Vector System: A Systematic Review. Viruses, 2023
- CRISPR-Cas9 Gene Therapy: Non-Viral Delivery and Stimuli-Responsive Nanoformulations. Molecules, 2025
- Advanced delivery systems for gene editing: A comprehensive review from the GenE-HumDi COST Action Working Group. Mol Ther Nucleic Acids, 2025
- In vivo delivery of CRISPR-Cas9 genome editing components for therapeutic applications. Biomaterials, 2022
- Mesoporous Nanoparticles for Diagnosis and Treatment of Liver Cancer in the Era of Precise Medicine. Pharmaceutics, 2022