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Updated: Jun 22, 2026
Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting
Published on: October 26, 2018
Designing adenoviral vectors for tumor-specific targeting
1Translational Research Laboratory, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain.
Abstract:
Adenovirus provides an attractive candidate tool to destroy tumor cells. However, to fulfill the expectations, selective targeting of tumor cells is mandatory. This chapter reviews critical aspects in the design of tumor-targeted adenovirus vectors and oncolytic adenoviruses. The review focuses on genetic modifications of capsid and regulatory genes that can enhance the therapeutic index of these agents after systemic administration. Selectivity will be considered at different levels: biodistribution selectivity of the injected virus particles, transductional selectivity defined as cell receptor interactions and trafficking that lead to virus gene expression, transcriptional selectivity by means of tumor-selective promoters, and mutation-rescue selectivity to achieve selective replication. Proper assays to analyze selectivity at these different levels are discussed. Finally, mutations and transgenes that can enhance the potency and efficacy of tumor-targeted adenoviruses from virocentric or immunocentric points of view will be presented.
Insights
Engineered adenoviruses show promise for destroying tumor cells. Genetic modifications enhance tumor targeting and therapeutic index for systemic administration, improving cancer treatment efficacy.
Area of Science:
- Oncolytic virotherapy
- Gene therapy
- Cancer research
Background:
- Adenoviruses are promising tools for tumor cell destruction.
- Selective targeting of tumor cells is crucial for effective adenovirus-based cancer therapy.
- Current strategies require optimization for systemic administration to improve the therapeutic index.
Purpose of the Study:
- To review critical aspects in the design of tumor-targeted adenovirus vectors and oncolytic adenoviruses.
- To focus on genetic modifications of capsid and regulatory genes for enhanced therapeutic index.
- To discuss selectivity at multiple levels and methods for analysis.
Main Methods:
- Review of genetic modifications in capsid and regulatory genes.
- Analysis of selectivity at biodistribution, transductional, transcriptional, and mutation-rescue levels.
- Discussion of assays for analyzing selectivity and enhancing potency/efficacy.
Main Results:
- Genetic modifications can enhance the therapeutic index of adenoviruses for systemic administration.
- Selectivity can be achieved through various strategies including receptor interactions, tumor-specific promoters, and replication control.
- Virocentric and immunocentric approaches can improve potency and efficacy.
Conclusions:
- Optimized genetic engineering of adenoviruses is key to achieving selective tumor targeting and enhanced oncolytic efficacy.
- Multi-level selectivity strategies are essential for safe and effective systemic delivery of oncolytic adenoviruses.
- Further research into virocentric and immunocentric modifications holds promise for improving cancer virotherapy.