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Updated: May 31, 2026

Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting
Published on: October 26, 2018
Current targeting strategies for adenovirus vectors in cancer gene therapy
1Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China.
Abstract:
Adenovirus vectors (Adv) are the most frequently used vectors in gene therapy research, especially in cancer gene therapy. However, despite encouraging preclinical and early clinical results, the successful clinical utility of gene therapy has not yet been fully realized. Challenges to clinical trial success for targeted Adv include inefficient Adv-mediated gene transfer (because many tumor cells lack Adv receptors), poor transduction in tumor tissues after systemic administration, accumulation and undesirable transgene expression in the liver. This review summarizes current targeting strategies for Adv to overcome these obstacles. Strategies include transductional selectivity through genetic modification of viral coat proteins, transcriptional selectivity by means of tumor-specific promoters, and selective biodistribution from conjugation with targeting ligands or polymers such as polyethylene glycol (PEG). Furthermore, combining selective biodistribution and active targeting ligands such as proteins, antibodies and peptides is an intriguing and promising approach that will also be covered in this review. These studies have provided new insights into our understanding of the utility of Adv in cancer gene therapy.
Insights
Adenovirus vectors (Adv) show promise in cancer gene therapy but face challenges. This review explores strategies like genetic modification and targeting ligands to improve Adv
Area of Science:
- Oncology
- Gene Therapy
- Virology
Background:
- Adenovirus vectors (Adv) are widely used in cancer gene therapy research.
- Despite preclinical success, clinical utility is limited by inefficient gene transfer, poor tumor transduction, and liver accumulation.
Purpose of the Study:
- To review current targeting strategies for Adv to overcome clinical limitations.
- To explore methods for enhancing Adv-mediated gene transfer and specificity in cancer therapy.
Main Methods:
- Genetic modification of viral coat proteins for transductional selectivity.
- Utilizing tumor-specific promoters for transcriptional selectivity.
- Conjugation with targeting ligands (e.g., PEG, antibodies, peptides) for selective biodistribution.
Main Results:
- Targeting strategies aim to improve Adv receptor-mediated entry into tumor cells.
- Tumor-specific promoters enhance transgene expression only in cancer cells.
- Ligand conjugation and combined approaches improve biodistribution and reduce off-target effects.
Conclusions:
- Targeting strategies are crucial for overcoming Adv limitations in cancer gene therapy.
- Combining selective biodistribution with active targeting ligands offers a promising approach.
- Further research into Adv targeting will enhance their clinical utility in treating cancer.
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