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Updated: May 22, 2026
Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting
Published on: October 26, 2018
Adenovirus receptors: implications for targeting of viral vectors
1Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå, Sweden. niklas.arnberg@climi.umu.se
Abstract:
Cancer, cardiovascular disease, and infectious diseases are all global health threats. To combat these diseases with gene therapies, adenovirus-based vectors have been developed. Although certain clinical trials appear successful, there is an obvious need to improve the efficacy of most adenovirus-based vectors. For the most commonly used vector (based on type 5; Ad5), a main problem is its accumulation in the liver, which can be attributed to interactions with specific host factors. The diverse tropism for types other than Ad5 implies that vectors based on alternative types could have advantages. The numerous interactions of different adenoviruses with host molecules - such as the recently identified desmoglein-2 receptor - may cause novel and unexpected obstacles, but also may provide possibilities for vectors based on alternative types. This review provides an update of new and previously known molecules that mediate cellular attachment of human adenoviruses and discusses how these may influence the targeting of adenovirus-based vectors.
Insights
Adenovirus vectors show promise for gene therapy against major diseases but face efficacy challenges. Exploring alternative adenovirus types and their unique host interactions may improve vector targeting and reduce side effects.
Area of Science:
- Gene Therapy
- Virology
- Molecular Biology
Background:
- Adenovirus-based vectors are crucial for gene therapy targeting global health threats like cancer and cardiovascular disease.
- Current adenovirus vectors, particularly Adenovirus type 5 (Ad5), exhibit limitations, including significant liver accumulation due to host factor interactions.
- Improving the efficacy and targeting of adenovirus vectors is essential for successful clinical applications.
Purpose of the Study:
- To review known and novel molecules mediating human adenovirus cellular attachment.
- To discuss how these molecular interactions influence the development of improved adenovirus-based gene therapy vectors.
- To explore the potential advantages of using adenovirus types other than Ad5 for enhanced vector targeting.
Main Methods:
- Literature review of scientific publications on adenovirus-host interactions.
- Analysis of molecular mechanisms governing adenovirus cellular entry and tropism.
- Discussion of receptor-ligand interactions, including desmoglein-2, in adenovirus binding.
Main Results:
- Identified diverse host molecules, including desmoglein-2, that mediate adenovirus attachment.
- Highlighted that different adenovirus types possess distinct tropisms due to varied host molecule interactions.
- Emphasized that understanding these interactions is key to overcoming current vector limitations.
Conclusions:
- Alternative adenovirus serotypes offer potential advantages over Ad5 vectors due to different tropism and host interactions.
- Targeting specific host molecules presents opportunities for novel vector design and improved gene therapy efficacy.
- Further research into adenovirus-host interactions is vital for advancing gene therapy vector development.
