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Efficient gene transfer of VSV-G pseudotyped retroviral vector to human brain tumor

Authors
 H Lee  ;  J J Song  ;  E Kim  ;  C-O Yun  ;  J Choi  ;  B Lee  ;  J Kim  ;  J W Chang  ;  J-H Kim 
Citation
 GENE THERAPY, Vol.8(4) : 268-273, 2001 
Journal Title
 GENE THERAPY 
ISSN
 0969-7128 
Issue Date
2001
MeSH
Brain Neoplasms/metabolism ; Brain Neoplasms/therapy* ; Cation Exchange Resins/pharmacology ; Cell Membrane/metabolism ; Cholesterol/analogs & derivatives ; Cholesterol/pharmacology ; Fatty Acids, Monounsaturated/pharmacology ; Genetic Therapy/methods* ; Genetic Vectors/administration & dosage* ; Hexadimethrine Bromide/pharmacology ; Humans ; Leukemia Virus, Murine/genetics* ; Lipids/pharmacology ; Phosphatidylserines/metabolism ; Protamines/pharmacology ; Quaternary Ammonium Compounds/pharmacology ; Transduction, Genetic* ; Tumor Cells, Cultured ; Vesicular stomatitis Indiana virus*
Keywords
retroviral vector ; transduction efficiency ; VSV-G ; phosphatidylserine ; brain tumor
Abstract
A retroviral vector constructed from the murine leukemia virus (MLV) can only express transgenes in cells undergoing mitosis, indicating its suitability as a delivery vehicle for cancer gene therapy. However, the transduction efficiency (TE) of retroviruses embedding endogenous envelope proteins in human cancer cells was found to be unsatisfactory. Recently, several research groups have demonstrated the feasibility of a retroviral vector pseudotyped with a vesicular stomatitis virus G (VSV-G) protein. In this study, the potential of VSV-G pseudotyped MLV-based retrovirus was examined as a delivery vehicle in a variety of human cancer cells including brain tumor cells in vitro and in vivo. The transduction efficiency of the 293T/G/GP/LacZ retrovirus in cell culture was superior in most cancer cells, particularly in brain tumor cells, compared with that of other retroviruses, such as PA317- or PG13-derived. The relative growth rate and phosphatidylserine expression level on the plasma membrane of target cells mainly influenced the transduction efficiency of VSV-G pseudotyped retrovirus, which suggested that both the relative growth rate and phosphatidylserine expression level were major determinants of TE. Furthermore, 293T/G/GP/LacZ could efficiently transduce human cancer cells regardless of the presence of chemical additives, whereas in other retroviruses, cationic chemical additives such as polybrene or liposomes were essential during virus infection. Finally, an average of 10% gene expression was routinely obtained exclusively in the tumor mass when 293T/G/GP/LacZ concentrated by simple ultracentrifugation was directly administrated to pre-established brain tumors in animal models (U251-N nu/nu mice or C6 Wistar rats). All told, the present study suggests that the VSV-G pseudotyped retrovirus is a suitable vector for brain tumor gene therapy.
Files in This Item:
T200103072.pdf Download
DOI
10.1038/sj.gt.3301390
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
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 Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Joo Hang(김주항)
Song, Jae Jin(송재진) ORCID logo https://orcid.org/0000-0001-8183-9550
Yun, Chae Ok(윤채옥)
Chang, Jin Woo(장진우) ORCID logo https://orcid.org/0000-0002-2717-0101
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/142809
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