Biodegradable silica nanoparticles for efficient linear DNA gene delivery

Fecha de publicación: 31/12/2024 Fecha Ahead of Print: 05/08/2024

Autores de IDIVAL

• 

  Andrés Ramos Valle

  Autor

• 

  Mónica López Fanarraga

  Autor

Autores ajenos al IDIVAL

• Kirst H

Unidades

• NANOMEDICINA

  

  Investigador Responsable

  Mónica López Fanarraga

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.

Keywords

• St & ouml;ber method; silica nanoparticles; gene delivery; DNA embedment; gene transfection