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dl-VSVG-LacZ, a VSV-G epitope incorporated adenoviurs exhibit marked enhancement in gene transduction efficiency

Authors
 Chae-Ok Yun  ;  Eun-A Cho  ;  Joo-Hang Kim  ;  Joo-Hyuk Sohn  ;  Eunhee Kim  ;  Dae-Bong Kang  ;  Jae-Jin Song 
Citation
 Human Gene Therapy, Vol.14(17) : 1643-1652, 2003 
Journal Title
 Human Gene Therapy 
ISSN
 1043-0342 
Issue Date
2003
Abstract
Recombinant adenovirus (Ad) has emerged as the vector system of choice in cancer gene therapy. Its full utility, however, has been limited because of the low efficiency of adenovirus-mediated gene transfer to cancer cells - the main reason being that cancer cells in general express inherently low levels of the coxsackie and adenovirus receptor (CAR) on their surface. Development of novel strategies to achieve adenovirus infection in a CAR-independent manner may help to overcome this limitation. To this end, we have generated a novel recombinant Ad, dl-VSVG-LacZ, that contains a fiber knob with intact CAR entry capability and an additional phosphatidylserine (PS) entry capability. This was achieved by incorporating the vesicular stomatitis virus glycoprotein (VSV-G) epitope onto the C terminus of the fiber knob. VSV-G is an envelope protein that facilitates the specificity for binding of the virus to PS moieties on the cellular plasma membrane. The newly tropism-expanded adenovirus, dl-VSVG-LacZ, showed a remarkable improvement (3- to 20-fold) in the delivery of LacZ to a variety of mammalian cells including those that were CAR deficient. The greatest improvement in gene transfer was observed in cells that were difficult to transduce with an untargeted Ad (wildtype fiber). Furthermore, treatment with dl-VSVG-LacZ significantly enhanced gene transfer in vivo when compared with control adenovirus that lacked the VSV-G epitope. Taken together, these studies demonstrate that the strategy to extend adenovirus tropism may greatly improve the utility of adenovirus in gene therapy applications.
Full Text
http://online.liebertpub.com/doi/abs/10.1089/104303403322542284
DOI
10.1089/104303403322542284
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
5. Research Institutes (연구소) > Institute for Cancer Research (암연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
김주항(Kim, Joo Hang)
손주혁(Sohn, Joo Hyuk) ORCID logo https://orcid.org/0000-0002-2303-2764
송재진(Song, Jae Jin) ORCID logo https://orcid.org/0000-0001-8183-9550
윤채옥(Yun, Chae Ok)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/113723
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