Previous Article | Next Article 
Journal of Virology, July 2001, p. 5913-5920, Vol. 75, No. 13
Department of Pediatrics, Division of Medical
Genetics,1 and Department of
Genetics,2 Duke University Medical Center,
Durham, North Carolina 27710
Received 3 November 2000/Accepted 6 April 2001
The 100K protein has a number of critical roles vital for
successful completion of the late phases of the adenovirus (Ad) life
cycle. We hypothesized that the introduction of deletions within the
100K gene would allow for the production of a series of new classes of
Ad vector, including one that is replication competent but blocked in
the ability to carry out many late-phase Ad functions. Such a vector
would have potential for several gene therapy applications, based upon
its ability to increase the copy number of the transgene encoded by the
vector (via genome replication) while decreasing the side effects
associated with Ad late gene expression. To efficiently produce
100K-deleted Ad ([100K
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.13.5913-5920.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Adenovirus Vectors with the 100K Gene Deleted and
Their Potential for Multiple Gene Therapy Applications
]Ad) vectors, an E1- and
100K-complementing cell line (K-16) was successfully isolated.
Transfection of an [E1,100K]Ad vector genome into the
K-16 cells readily yielded high titers of the vector. After infection
of noncomplementing cells, we demonstrated that [100K]Ad vectors have a significantly decreased ability to express several Ad
late genes. Additionally, if the E1 gene was present in the infected
noncomplementing cells, [100K]Ad vectors were capable of
replicating their genomes to high copy number, but were significantly blocked in their ability to efficiently encapsidate the replicated genomes. Injection of an [E1,100K]Ad vector in vivo
also correlated with significantly decreased hepatotoxicity, as well as
prolonged vector persistence. In summary, the unique properties of
[100K]Ad vectors suggest that they may have utility in a
variety of gene therapy applications.
*
Corresponding author. Mailing address: Box 2618, MSRB,
Duke University Medical Center, Durham, NC 27710. Phone: (919)
681-6356. Fax: (919) 684-2362. E-mail:
amalf001{at}mc.duke.edu.
Journal of Virology, July 2001, p. 5913-5920, Vol. 75, No. 13
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.13.5913-5920.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Koyuncu, O. O., Dobner, T.
(2009). Arginine Methylation of Human Adenovirus Type 5 L4 100-Kilodalton Protein Is Required for Efficient Virus Production. J. Virol.
83: 4778-4790
[Abstract] [Full Text] -
Appledorn, D. M., Patial, S., McBride, A., Godbehere, S., Van Rooijen, N., Parameswaran, N., Amalfitano, A.
(2008). Adenovirus Vector-Induced Innate Inflammatory Mediators, MAPK Signaling, As Well As Adaptive Immune Responses Are Dependent upon Both TLR2 and TLR9 In Vivo. J. Immunol.
181: 2134-2144
[Abstract] [Full Text] -
Hartman, Z. C., Kiang, A., Everett, R. S., Serra, D., Yang, X. Y., Clay, T. M., Amalfitano, A.
(2007). Adenovirus Infection Triggers a Rapid, MyD88-Regulated Transcriptome Response Critical to Acute-Phase and Adaptive Immune Responses In Vivo. J. Virol.
81: 1796-1812
[Abstract] [Full Text] -
Roberts, M. L., Wells, D. J., Graham, I. R., Fabb, S. A., Hill, V. J., Duisit, G., Yuasa, K., Takeda, S.'i., Cosset, F.-L., Dickson, G.
(2002). Stable micro-dystrophin gene transfer using an integrating adeno-retroviral hybrid vector ameliorates the dystrophic pathology in mdx mouse muscle. Hum Mol Genet
11: 1719-1730
[Abstract] [Full Text]
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»