Document Detail


General strategy for broadening adenovirus tropism.
MedLine Citation:
PMID:  14512557     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Laura Fontana; Maurizio Nuzzo; Lorena Urbanelli; Paolo Monaci
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of virology     Volume:  77     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-09-26     Completed Date:  2003-10-23     Revised Date:  2011-07-01    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11094-104     Citation Subset:  IM    
Affiliation:
Department of Molecular & Cell Biology, I.R.B.M. P. Angeletti, Pomezia, Rome, Italy.
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MeSH Terms
Descriptor/Qualifier:
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:
0/CXADR-like membrane protein; 0/Capsid Proteins; 0/Peptide Library; 0/Receptors, Virus; 0/hexon capsid protein, Adenovirus
Comments/Corrections

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