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Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting
Published on: October 26, 2018
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Retargeted adenoviruses for radiation-guided gene delivery
S A Kaliberov1,2, L N Kaliberova1,2, H Yan1,2
1Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO, USA.
Cancer Gene Therapy
|August 6, 2016
Summary
Researchers developed a novel gene delivery method for glioblastoma by modifying adenoviruses with a peptide targeting radiation-induced proteins. This approach enhances tumor-specific gene expression in irradiated tumors, improving therapeutic potential.
Area of Science:
- Oncolytic virotherapy
- Gene therapy
- Cancer research
Background:
- Glioblastoma treatment can be improved by combining radiation with gene delivery or oncolytic viruses.
- Radiation therapy induces molecular changes in cancer cells, including overexpression of 78 kDa glucose-regulated protein (GRP78) on cancer and endothelial cells.
- Targeting radiation-inducible proteins offers a strategy for enhanced tumor specificity in gene delivery.
Purpose of the Study:
- To improve tumor-specific adenovirus-mediated gene delivery by targeting the radiation-inducible GRP78.
- To evaluate the utility of a GRP78-binding peptide for retargeting adenoviruses.
Main Methods:
- Developed fiber-modified adenoviruses with a GRP78-binding peptide inserted into the fiber-fibritin.
- Evaluated reporter gene expression in vitro using glioma cells and in vivo using a D54MG tumor xenograft model.
- Utilized an adenoviral fiber replacement approach for peptide insertion and targeting.
Main Results:
- Fiber-modified adenoviruses demonstrated increased reporter gene expression in irradiated tumors compared to untreated tumors.
- The GRP78-binding peptide enhanced gene delivery specifically to radiation-responsive tumor cells.
- Successful retargeting of adenoviruses was achieved using the GRP78-binding peptide.
Conclusions:
- Adenoviral retargeting using a GRP78-binding peptide is feasible for enhancing gene delivery to radiation-treated glioblastoma.
- This strategy selectively targets tumor cells responding to radiation, offering a promising approach for glioblastoma therapy.
- The developed fiber-modified adenoviruses show potential for improving therapeutic outcomes in glioblastoma treatment.
