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Adenoviral Expression System (adenoviral + expression_system)

Distribution by Scientific Domains
Life Sciences100%

Selected Abstracts

Altering DNA base excision repair: Use of nuclear and mitochondrial-targeted N -methylpurine DNA glycosylase to sensitize astroglia to chemotherapeutic agents,

GLIA, Issue 14 2007
Jason F. Harrison
Abstract Primary astrocyte cultures were used to investigate the modulation of DNA repair as a tool for sensitizing astrocytes to genotoxic agents. Base excision repair (BER) is the principal mechanism by which mammalian cells repair alkylation damage to DNA and involves the processing of relatively nontoxic DNA adducts through a series of cytotoxic intermediates during the course of restoring normal DNA integrity. An adenoviral expression system was employed to target high levels of the BER pathway initiator, N -methylpurine glycosylase (MPG), to either the mitochondria or nucleus of primary astrocytes to test the hypothesis that an alteration in BER results in increased alkylation sensitivity. Increasing MPG activity significantly increased BER kinetics in both the mitochondria and nuclei. Although modulating MPG activity in mitochondria appeared to have little effect on alkylation sensitivity, increased nuclear MPG activity resulted in cell death in astrocyte cultures treated with methylnitrosourea (MNU). Caspase-3 cleavage was not detected, thus indicating that these alkylation sensitive astrocytes do not undergo a typical programmed cell death in response to MNU. Astrocytes were found to express relatively high levels of antiapoptotic Bcl-2 and Bcl-XL and very low levels of proapoptotic Bad and Bid suggesting that the mitochondrial pathway of apoptosis may be blocked making astrocytes less vulnerable to proapoptotic stimuli compared with other cell types. Consequently, this unique characteristic of astrocytes may be responsible, in part, for resistance of astrocytomas to chemotherapeutic agents. © 2007 Wiley-Liss, Inc. [source]

Retracted: A new inducible adenoviral expression system that responds to inflammatory stimuli in vivo (J Gene Med 2006; 8(12): 1369,1378)

THE JOURNAL OF GENE MEDICINE, Issue 5 2007
Article first published online: 1 MAY 200
This paper, by Gang Cai, Xiaomeng Nie, Pin'e Guo, Zheng Guan, Jun Zhang and Qian Shen (DOI: 10.1002/jgm.983) has been retracted by agreement between the journal Editors and John Wiley & Sons, Ltd. The retraction has been agreed due to overlap with text from "An inflammation-inducible adenoviral expression system for local treatment of the arthritic joint" by van de Loo FAJ, de Hooge ASK, Smeets RL, Bakker AC, Bennink MB, Arntz OJ, Joosten LAB, van Beuningen HM, van der Kraan PK, Varley AW and van den Berg WB (Gene Therapy 2004; 11: 581,590) and other published papers. There is also similarity of experimental design compared to the van de Loo et al. paper, which was not cited by Cai et al. [source]

A new inducible adenoviral expression system that responds to inflammatory stimuli in vivo

THE JOURNAL OF GENE MEDICINE, Issue 12 2006
Gang Cai
Abstract Background Gene transfer using inducible promoters, which control expression of transgenic proteins in response to physiological conditions, may have significant advantages. In this study, we tried to achieve an inducible adenoviral expression system for physiologically responsive gene therapy of autoimmune or inflammatory diseases. Methods A luciferase reporter vector with a hybrid promoter containing the human IL-1, enhancer region (,3690 to , 2720) and the human CIITA promoter IV (,399 to + 2) was constructed. A replication-deficient adenovirus was engineered with luciferase controlled by the IL1,/CIITApIV promoter (Ad-IL1,/CIITApIV-Luc). The reporter vector or adenovirus was transfected to C57Bl/6 myeloid dendritic cells (DCs), RAW264.7, and Hep G2 to study the in vitro characteristics of this hybrid promoter. An inflammation model was prepared by injecting lipopolysaccharide (LPS) into Balb/c mice intraperitoneally (i.p.), and infected with Ad-IL1,/CIITApIV-Luc or Ad-CMV-Luc to study the in vivo characteristics of the IL1,/CIITApIV promoter. Results The IL1,/CIITApIV hybrid promoter has pronounced promoter activity, broad-range responsiveness to cytokines or LPS, and can be rechallenged after first induction. In the inflammation model, IL1,/CIITApIV could drive hepatic luciferase expression increasedly rapidly after LPS challenge and in a LPS dose-dependent manner. Conclusions Using the IL1,/CIITApIV hybrid promoter in gene transfer vectors may make it possible to produce transgenic proteins in vivo in direct relationship with the intensity and duration of an individual's status. By providing endogenously controlled production of transgenic proteins, this approach might limit the severity of autoimmune or inflammatory response without interfering with the beneficial components of host defense and immunity. Copyright © 2006 John Wiley & Sons, Ltd. [source]