Enhancing Cytoplasmic Expression of Exogenous mRNA Through Dynamic Mechanical Stimulation.

Autor: Chen J; Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, 07030, USA., Patel A; Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, 07030, USA., Mir M; Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, 07030, USA., Hudock MR; Department of Biomedical Engineering, Columbia University, New York, NY, 10032, USA., Pinezich MR; Department of Biomedical Engineering, Columbia University, New York, NY, 10032, USA., Guenthart B; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, 94304, USA., Bacchetta M; Department of Cardiac Surgery, Vanderbilt University, Nashville, TN, 37232, USA.; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37232, USA., Vunjak-Novakovic G; Department of Biomedical Engineering, Columbia University, New York, NY, 10032, USA., Kim J; Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, 07030, USA.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2024 Oct 23, pp. e2401918. Date of Electronic Publication: 2024 Oct 23.
DOI: 10.1002/adhm.202401918
Abstrakt: Ionizable lipid nanoparticles (LNPs) are pivotal in combating COVID-19, and numerous preclinical and clinical studies have highlighted their potential in nucleic acid-based therapies and vaccines. However, the effectiveness of endosomal escape for the nucleic acid cargos encapsulated in LNPs is still low, leading to suboptimal treatment outcomes and side effects. Hence, improving endosomal escape is crucial for enhancing the efficacy of nucleic acid delivery using LNPs. Here, a mechanical oscillation (frequency: 65 Hz) is utilized to prompt the LNP-mediated endosomal escape. The results reveal this mechanical oscillation can induce the combination and fusion between LNPs with opposite surface charges, enhance endosomal escape of mRNA, and increase the transfection efficiency of mRNA. Additionally, cell viability remains high at 99.3% after treatment with oscillation, which is comparable to that of untreated cells. Furthermore, there is no obvious damage to mitochondrial membrane potential and Golgi apparatus integrity. Thus, this work presents a user-friendly and safe approach to enhancing endosomal escape of mRNA and boosting gene expression. As a result, this work can be potentially utilized in both research and clinical fields to facilitate LNP-based delivery by enabling more effective release of LNP-encapsulated cargos from endosomes.
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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