@article{10902/34494,
year = {2024},
url = {https://hdl.handle.net/10902/34494},
abstract = {Targeting, safety, scalability, and storage stability of vectors are still challenges in the field of nucleic acid delivery for gene therapy. Silica-based nanoparticles have been widely studied as gene carriers, exhibiting key features such as biocompatibility, simplistic synthesis, and enabling easy surface modifications for targeting. However, the ability of the formulation to incorporate DNA is limited, which restricts the number of DNA molecules that can be incorporated into the particle, thereby reducing gene expression. Here we use polymerase chain reaction (PCR)-generated linear DNA molecules to augment the coding sequences of gene-carrying nanoparticles, thereby maximizing nucleic acid loading and minimizing the size of these nanocarriers. This approach results in a remarkable 16-fold increase in protein expression six days post-transfection in cells transfected with particles carrying the linear DNA compared with particles bearing circular plasmid DNA. The study also showed that the use of linear DNA entrapped in DNA@SiO₂ resulted in a much more efficient level of gene expression compared to standard transfection reagents. The system developed in this study features simplicity, scalability, and increased transfection efficiency and gene expression over existing approaches, enabled by improved embedment capabilities for linear DNA, compared to conventional methods such as lipids or polymers, which generally show greater transfection efficiency with plasmid DNA. Therefore, this novel methodology can find applications not only in gene therapy but also in research settings for high-throughput gene expression screenings.},
organization = {Funding: MLF acknowledges the financial support from the Spanish Instituto de Salud Carlos iii, and the European Union FEDER funds under Projects ref. PI22/00030, co-funded by the European Regional Development Fund, ‘Investing in your future’ and Grant TED2021-129248B-100, the Maria Zambrano Fellowship RMZ-015 funded by MCIN/AEI/10.13039/ 501100011033 and by the ‘European Union Next Generation EU/PRTR.’ We also thank the Gobierno Regional de Cantabria and IDIVAL for the project Refs IDI 20/22, INNVAL21/19, NEXTVAL 22/12, and IDI-020-022. The figures and graphs have been created with BioRender software (BioRender.com, License ID: 9519A1C8-0002).},
publisher = {Taylor & Francis},
publisher = {Drug Delivery, 2024, 31(1), 2385376},
title = {Biodegradable silica nanoparticles for efficient linear DNA gene delivery},
author = {Ramos Valle, Andrés and Kirst, Henning and López Fanarraga, Mónica},
}