ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
Modifications of adenovirus hexon allow for either hepatocyte detargeting or targeting with potential evasion from Kupffer cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 77 citations in OpenAlex.
- Review
- Review
- The use of adenoviral vectors in gene therapy and vaccine approaches.Genetics and molecular biology · 2022Article
- Immunovirotherapy: The role of antibody based therapeutics combination with oncolytic viruses.Frontiers in immunology · 2022Review
- Genetic and Chemical Capsid Modifications of Adenovirus Vectors to Modulate Vector-Host Interactions.Viruses · 2021Review
- Nonreplicating Adenoviral Vectors: Improving Tropism and Delivery of Cancer Gene Therapy.Cancers · 2021Review
- Capsid and Genome Modification Strategies to Reduce the Immunogenicity of Adenoviral Vectors.International journal of molecular sciences · 2021Review
- Superimposition of Viral Protein Structures: A Means to Decipher the Phylogenies of Viruses.Viruses · 2020Review
- Review
- Retargeting adenoviruses for therapeutic applications and vaccines.FEBS letters · 2020Review
- High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy.International journal of molecular sciences · 2020Review
- Critical considerations for targeting colorectal liver metastases with nanotechnology.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2020Review
- CAV-2 Vector Development and Gene Transfer in the Central and Peripheral Nervous Systems.Frontiers in molecular neuroscience · 2019Review
- Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting.Journal of visualized experiments : JoVE · 2018Article
- Oncolytic viruses: adenoviruses.Virus genes · 2017Review
- Gene therapy with helper-dependent adenoviral vectors: lessons from studies in large animal models.Virus genes · 2017Review
- Barriers to systemic application of virus-based vectors in gene therapy: lessons from adenovirus type 5.Virus genes · 2017Review
- Article
- CXCL12 retargeting of an adenovirus vector to cancer cells using a bispecific adapter.Oncolytic virotherapy · 2016Article
- Oncolytic Adenovirus: Strategies and Insights for Vector Design and Immuno-Oncolytic Applications.Viruses · 2015Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
In vivo gene transfer with adenovirus vectors would significantly benefit from a tight control of the adenovirus-inherent liver tropism. For efficient hepatocyte transduction, adenovirus vectors need to evade from Kupffer cell scavenging while delivery to peripheral tissues or tumors could be improved if both scavenging by Kupffer cells and uptake by hepatocytes were blocked. Here, we provide evidence that a single point mutation in the hexon capsomere designed to enable defined chemical capsid modifications may permit both detargeting from and targeting to hepatocytes with evasion from Kupffer cell scavenging. Vector particles modified with small polyethylene glycol (PEG) moieties specifically on hexon exhibited decreased transduction of hepatocytes by shielding from blood coagulation factor binding. Vector particles modified with transferrin or, surprisingly, 5,000 Da PEG or dextran increased hepatocyte transduction up to 18-fold independent of the presence of Kupffer cells. We further show that our strategy can be used to target high-capacity adenovirus vectors to hepatocytes emphasizing the potential for therapeutic liver-directed gene transfer. Our approach may lead to a detailed understanding of the interactions between adenovirus vectors and Kupffer cells, one of the most important barriers for adenovirus-mediated gene delivery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.