ArticleProceedings of the National Academy of Sciences of the United States of America2013
Development of a generic adenovirus delivery system based on structure-guided design of bispecific trimeric DARPin adapters.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 87 citations in OpenAlex.
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- Genome-replicating HC-AdV: A novel high-capacity adenoviral vector class featuring enhancedMolecular therapy. Methods & clinical development · 2025Article
- Selective targeting of TBXT with DARPins identifies regulatory networks and therapeutic vulnerabilities in chordoma.Science advances · 2025Article
- Dendritic cell targeting in lymph nodes with modular adapters boosts HAdV5 and HC-HAdV5 tumor vaccination by co-secretion of IL-2v and IL-21.Molecular therapy. Oncology · 2025Article
- Article
- Activated blood-derived human primary T cells support replication of HAdV C5 and virus transmission to polarized human primary epithelial cells.Journal of virology · 2025Article
- DARPin-fused T cell engager for adenovirus-mediated cancer therapy.Molecular therapy. Oncology · 2024Article
- Designed Ankyrin Repeat Proteins as Actin Labels of Distinct Cytoskeletal Structures in Living Cells.ACS nano · 2024Article
- Targeted shock-and-kill HIV-1 gene therapy approach combining CRISPR activation, suicide gene tBid and retargeted adenovirus delivery.Gene therapy · 2024Article
- FAP-retargeted Ad5 enables in vivo gene delivery to stromal cells in the tumor microenvironment.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Targeted adenovirus-mediated transduction of human T cellsMolecular therapy. Methods & clinical development · 2023Article
- Combining of Oncolytic Virotherapy and Other Immunotherapeutic Approaches in Cancer: A Powerful Functionalization Tactic.Global challenges (Hoboken, NJ) · 2023Review
- CRISPR-mediated MECOM depletion retards tumor growth by reducing cancer stem cell properties in lung squamous cell carcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Engineering Cancer Selective Virotherapies: Are the Pieces of the Puzzle Falling into Place?Human gene therapy · 2022Review
- Review
- Fiber manipulation and post-assembly nanobody conjugation for adenoviral vector retargeting through SpyTag-SpyCatcher protein ligation.Frontiers in molecular biosciences · 2022Article
- Distinct conformations of the HIV-1 V3 loop crown are targetable for broad neutralization.Nature communications · 2021Article
- The SHREAD gene therapy platform for paracrine delivery improves tumor localization and intratumoral effects of a clinical antibody.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Nonreplicating Adenoviral Vectors: Improving Tropism and Delivery of Cancer Gene Therapy.Cancers · 2021Review
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Adenoviruses (Ads) have shown promise as vectors for gene delivery in clinical trials. Efficient viral targeting to a tissue of choice requires both ablation of the virus' original tropism and engineering of an efficient receptor-mediated uptake by a specific cell population. We have developed a series of adapters binding to the virus with such high affinity that they remain fully bound for >10 d, block its natural receptor binding site and mediate interaction with a surface receptor of choice. The adapter contains two fused modules, both consisting of designed ankyrin repeat proteins (DARPins), one binding to the fiber knob of adenovirus serotype 5 and the other binding to various tumor markers. By solving the crystal structure of the complex of the trimeric knob with three bound DARPins at 1.95-Å resolution, we could use computer modeling to design a link to a trimeric protein of extraordinary kinetic stability, the capsid protein SHP from the lambdoid phage 21. We arrived at a module which binds the knob like a trimeric clamp. When this clamp was fused with DARPins of varying specificities, it enabled adenovirus serotype 5-mediated delivery of a transgene in a human epidermal growth factor receptor 2-, epidermal growth factor receptor-, or epithelial cell adhesion molecule-dependent manner with transduction efficiencies comparable to or even exceeding those of Ad itself. With these adapters, efficiently produced in Escherichia coli, Ad can be converted rapidly to new receptor specificities using any ligand as the receptor-binding moiety. Prefabricated Ads with different payloads thus can be retargeted readily to many cell types of choice.
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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.