[논문]Enhancement of Gene Delivery to Cancer Cells by a Retargeted Adenovirus

Oh Kwang Seok; Engler Jeffrey A.; Joung In Sil

Enhancement of Gene Delivery to Cancer Cells by a Retargeted Adenovirus 원문보기

The journal of microbiology, v.43 no.2, 2005년, pp.179 - 182

Oh Kwang Seok (Department of Biology, Hanseo University) , Engler Jeffrey A. (Departments of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham) , Joung In Sil (Department of Biology, Hanseo University)

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The inefficiency of in vivo gene transfer using currently available vectors reflects a major hurdle in cancer gene therapy. Both viral and non-viral approaches that improve gene transfer efficiency have been described, but suffer from a number of limitations. Herein, a fiber-modified adenovirus, carrying the small peptide ligand on the capsid, was tested for the delivery of a transgene to cancer cells. The fiber-modified adenovirus was able to mediate the entry and expression of a $\beta$-galactosidase into cancer cells with increased efficiency compared to the unmodified adenovirus. Particularly, the gene transfer efficiency was improved up to 5 times in OVCAR3 cells, an ovarian cancer cell line. Such transduction systems hold promise for delivering genes to transferrin receptor overexpressing cancer cells, and could be used for future cancer gene therapy.

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fiber's trimer formation, with only very low yields of viruses when grown in 293 cells (data not shown). The integrity of the recombinant virus was checked, using the isolated viral DNA, before performing further experiments. The presence of the sequence encoding the Tf-peptide fused to fiber gene was verified by polymerase chain reaction with the primers of corresponding sequences for the Tf-peptide and upstream fiber gene (Fig.
, 2002). The strategy used in this study was easy to manipulate, and produced high yields of viruses. In addition, the gene delivery by fiber-modified viruses would not be affected by serum transferrin since the ligand binds to a different site that of native transferrin.

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Enzyme activities in the lysates from AdLac infected cells were set to 1 (open bar) and those detected in Tf- AdLac infected cells are shown as fold increases (hatched bar). The MOI used in these experiments was 10, with the exception of the 293 cells (which was 1).

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