| General strategy for broadening adenovirus tropism. | |
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MedLine Citation:
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PMID: 14512557 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 lambda 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. |
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Authors:
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Laura Fontana; Maurizio Nuzzo; Lorena Urbanelli; Paolo Monaci |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of virology Volume: 77 ISSN: 0022-538X ISO Abbreviation: J. Virol. Publication Date: 2003 Oct |
Date Detail:
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Created Date: 2003-09-26 Completed Date: 2003-10-23 Revised Date: 2011-07-01 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 11094-104 Citation Subset: IM |
Affiliation:
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Department of Molecular & Cell Biology, I.R.B.M. P. Angeletti, Pomezia, Rome, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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3T3 Cells Adenoviridae / physiology* Animals Bacteriophage lambda / genetics CHO Cells Capsid Proteins / physiology* Cricetinae Dendritic Cells / physiology Gene Transfer, Horizontal Genetic Vectors Humans Mice Peptide Library Receptors, Virus / metabolism Transduction, Genetic Tropism |
| Chemical | |
Reg. No./Substance:
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0/CXADR-like membrane protein; 0/Capsid Proteins; 0/Peptide Library; 0/Receptors, Virus; 0/hexon capsid protein, Adenovirus |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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