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Journal of Virology, December 2003, p. 12881-12885, Vol. 77, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.23.12881-12885.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Development and Characterization of Novel Empty Adenovirus Capsids and Their Impact on Cellular Gene Expression

Jackie L. Stilwell,¹ Douglas M. McCarty,¹ Atsuko Negishi,² Richard Superfine,² and R. Jude Samulski^1,3*

UNC Gene Therapy Center,¹ Department of Physics and Astronomy,² Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599³

Received 9 May 2003/ Accepted 5 September 2003

Adenovirus (Ad) has been extensively studied as a eukaryotic viral vector. As these vectors have evolved from first-generation vectors to vectors that contain either very few or no viral genes ("gutless" Ad), significant reductions in the host innate immune response upon infection have been observed. Regardless of these vector improvements an unknown amount of toxicity has been associated with the virion structural proteins. Here we demonstrate the ability to generate high particle numbers (10¹¹ to 10¹²) of Ad empty virions based on a modification of Cre/lox gutless Ad vectors. Using a battery of analyses (electron microscopy, atomic force microscopy, confocal images, and competition assays) we characterized this reagent and determined that it (i) makes intact virion particles, (ii) competes for receptor binding with wild-type Ad, and (iii) enters the cell proficiently, demonstrating an ability to carry out essential steps of viral entry. To further study the biological impact of these Ad empty virions on infected cells, we carried out DNA microarray analysis. Compared to that for recombinant Ad, the number of mRNAs modulated upon infection was significantly reduced but the expression signatures were similar. This reagent provides a valuable tool for studies of Ad in that researchers can examine the effect of infection in the presence of the virion capsid alone.

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* Corresponding author. Mailing address: UNC Gene Therapy Center, University of North Carolina, CB# 7352, Chapel Hill, NC 27514. Phone: (919) 962-3285. Fax: (919) 966-0907. E-mail: rjs{at}med.unc.edu.

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Journal of Virology, December 2003, p. 12881-12885, Vol. 77, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.23.12881-12885.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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