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Journal of Virology, January 2000, p. 354-362, Vol. 74, No. 1
Department of Immunology, Scripps Research
Institute, La Jolla, California 92037,1 and
Genetic Therapy, Inc., Gaithersburg, Maryland
208782
Received 8 June 1999/Accepted 22 September 1999
While adenovirus (Ad) gene delivery vectors are useful in many gene
therapy applications, their broad tropism means that they cannot be
directed to a specific target cell. There are also a number of cell
types involved in human disease which are not transducible with
standard Ad vectors, such as Epstein-Barr virus (EBV)-transformed B
lymphocytes. Adenovirus binds to host cells via the viral fiber protein, and Ad vectors have previously been retargeted by modifying the fiber gene on the viral chromosome. This requires that the modified
fiber be able to bind to the cell in which the vector is grown, which
prevents truly specific vector targeting. We previously reported a gene
delivery system based on a fiber gene-deleted Ad type 5 (Ad5) vector
(Ad5.
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Adenovirus Vector Pseudotyping in Fiber-Expressing
Cell Lines: Improved Transduction of Epstein-Barr Virus-Transformed
B Cells
gal.
F) and packaging cells that express the viral fiber
protein. Expression of different fibers in packaging cells will allow
Ad retargeting without modifying the viral chromosome. Importantly,
fiber proteins which can no longer bind to the producer cells can also
be used. Using this approach, we generated for the first time
pseudotyped Ad5.
gal.
F particles containing either the wild-type
Ad5 fiber protein or a chimeric fiber with the receptor-binding knob
domain of the Ad3 fiber. Particles equipped with the chimeric fiber
bound to the Ad3 receptor rather than the coxsackievirus-adenovirus
receptor protein used by Ad5. EBV-transformed B lymphocytes were
infected efficiently by the Ad3-pseudotyped particles but poorly by
virus containing the Ad5 fiber protein. The strategy described here represents a broadly applicable method for targeting gene delivery to
specific cell types.
*
Corresponding author. Mailing address: Department of
Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-8072. Fax: (858) 784-8472. E-mail:
gnemerow{at}scripps.edu.
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