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Updated: Jul 2, 2026
Vascular Gene Transfer from Metallic Stent Surfaces Using Adenoviral Vectors Tethered through Hydrolysable Cross-linkers
Published on: August 12, 2014
Extended release of adenovirus from silica implants in vitro and in vivo
L Kangasniemi1, M Koskinen, M Jokinen
1Cancer Gene Therapy Group, Molecular Cancer Biology Program and Transplantation Laboratory, University of Helsinki, Helsinki, Finland.
Abstract:
Despite promising preclinical results, the clinical benefits of cancer gene therapy have been modest heretofore. The main obstacle continues to be the level and persistence of gene delivery to sufficiently large areas of the tumor. One approach for overcoming this might entail extended local virus release. We studied the utility of silica gel monoliths for delivery of adenovirus to advanced orthotopic gastric and pancreatic cancer tumors. Initially, the biochemical properties of the silica-virus matrix were studied and nearly linear release as a function of time was detected. Virus stayed infective for weeks at +37 degrees C and months at +4 degrees C, which may facilitate storage and distribution. In vivo, extended release of functional replication deficient and also replication-competent, capsid-modified oncolytic viruses was seen. Treatment of mice with pancreatic cancer doubled their survival (P<0.001). Also, silica gel-based delivery slowed the development of antiadenovirus antibodies.
Insights
Silica gel monoliths enable sustained adenovirus delivery for cancer gene therapy, improving survival in pancreatic cancer models and reducing immune response.
Area of Science:
- Biomedical Engineering
- Oncology
- Gene Therapy
Background:
- Cancer gene therapy faces challenges with gene delivery level and persistence.
- Overcoming these limitations may involve extended local virus release strategies.
Purpose of the Study:
- To evaluate silica gel monoliths for adenovirus delivery in gastric and pancreatic cancer.
- To assess the stability and release kinetics of adenovirus from silica gel.
- To determine the in vivo efficacy and immunogenicity of this delivery system.
Main Methods:
- Biochemical analysis of silica-virus matrix properties.
- In vitro assessment of virus infectivity at different temperatures.
- In vivo studies using orthotopic gastric and pancreatic cancer models in mice.
- Evaluation of virus release, tumor survival, and antibody development.
Main Results:
- Silica gel demonstrated nearly linear virus release over time.
- Adenovirus remained infective after prolonged storage at +37°C and +4°C.
- Extended release of functional adenoviruses (replication-deficient and oncolytic) was observed in vivo.
- Pancreatic cancer tumor growth was significantly impacted, doubling mouse survival (P<0.001).
- Silica gel delivery attenuated the development of anti-adenovirus antibodies.
Conclusions:
- Silica gel monoliths are a viable platform for sustained adenovirus delivery in cancer gene therapy.
- This approach enhances therapeutic efficacy and potentially mitigates adverse immune responses.
- The findings support further investigation of silica gel-based viral vector delivery for solid tumors.
