General Strategy for Broadening Adenovirus Tropism
| Autor: | Maurizio Nuzzo, Lorena Urbanelli, Laura Fontana, Paolo Monaci |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Coxsackie and Adenovirus Receptor-Like Membrane Protein
Cell type Gene Transfer Horizontal viruses Genetic Vectors Immunology CHO Cells Biology medicine.disease_cause Tropism Microbiology 3T3 cells Adenoviridae Mice Peptide Library Transduction Genetic Cricetinae Virology medicine Animals Humans Peptide library Chinese hamster ovary cell 3T3 Cells Dendritic Cells Gene Therapy Bacteriophage lambda Molecular biology medicine.anatomical_structure Capsid Cell culture Insect Science Receptors Virus Capsid Proteins |
| Zdroj: | Journal of Virology. 77:11094-11104 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.77.20.11094-11104.2003 |
| Popis: | In spite of its broad host range, adenovirus type 5 (Ad5) transduces a number of clinically relevant tissues and cell types inefficiently, mostly because of low expression of the coxsackievirus-adenovirus receptor (CAR). To improve gene transfer to such cells, we modified the Ad5 fiber knob to recognize novel receptors. We expressed a functional Ad5 fiber knob domain on the capsid of phage λ and employed this display system to construct a large collection of ligands in the HI loop of the Ad5 knob. Panning this library on the CAR-negative mouse fibroblast cell line NIH 3T3 resulted in the identification of three clones with increased binding to these cells. Adenoviruses incorporating these ligands in the fiber gene transduced NIH 3T3 cells 2 or 3 orders of magnitude better than the parent vector. The same nonnative tropism was revealed in other cell types, independently of CAR expression. These Ad5 derivatives proved capable of transducing mouse and human primary immature dendritic cells with up to 100-fold increased efficiency. |
| Databáze: | OpenAIRE |
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