Biodegradable silica nanoparticles for efficient linear DNA gene delivery
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 eas...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Drug Delivery |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2024.2385376 |
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| author | Andrés Ramos-Valle Henning Kirst Mónica L. Fanarraga |
| author_facet | Andrés Ramos-Valle Henning Kirst Mónica L. Fanarraga |
| author_sort | Andrés Ramos-Valle |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6838e9b5f8eb4004a690b0b67f88e9b3 |
| institution | OA Journals |
| issn | 1071-7544 1521-0464 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj-art-6838e9b5f8eb4004a690b0b67f88e9b32025-08-20T02:38:11ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642024-12-0131110.1080/10717544.2024.2385376Biodegradable silica nanoparticles for efficient linear DNA gene deliveryAndrés Ramos-Valle0Henning Kirst1Mónica L. Fanarraga2The Nanomedicine Group, Institute Valdecilla-IDIVAL, Santander, SpainThe Nanomedicine Group, Institute Valdecilla-IDIVAL, Santander, SpainThe Nanomedicine Group, Institute Valdecilla-IDIVAL, Santander, SpainTargeting, 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.https://www.tandfonline.com/doi/10.1080/10717544.2024.2385376Stöber methodsilica nanoparticlesgene deliveryDNA embedmentgene transfection |
| spellingShingle | Andrés Ramos-Valle Henning Kirst Mónica L. Fanarraga Biodegradable silica nanoparticles for efficient linear DNA gene delivery Drug Delivery Stöber method silica nanoparticles gene delivery DNA embedment gene transfection |
| title | Biodegradable silica nanoparticles for efficient linear DNA gene delivery |
| title_full | Biodegradable silica nanoparticles for efficient linear DNA gene delivery |
| title_fullStr | Biodegradable silica nanoparticles for efficient linear DNA gene delivery |
| title_full_unstemmed | Biodegradable silica nanoparticles for efficient linear DNA gene delivery |
| title_short | Biodegradable silica nanoparticles for efficient linear DNA gene delivery |
| title_sort | biodegradable silica nanoparticles for efficient linear dna gene delivery |
| topic | Stöber method silica nanoparticles gene delivery DNA embedment gene transfection |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2024.2385376 |
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