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Title: Systemic delivery of fusogenic membrane glycoprotein-expressing neural stem cells to selectively kill tumor cells
Authors: Zhu, D.
Lam, D.H.
Purwanti, Y.I.
Goh, S.L.
Wu, C.
Zeng, J.
Fan, W.
Wang, S. 
Issue Date: Aug-2013
Citation: Zhu, D., Lam, D.H., Purwanti, Y.I., Goh, S.L., Wu, C., Zeng, J., Fan, W., Wang, S. (2013-08). Systemic delivery of fusogenic membrane glycoprotein-expressing neural stem cells to selectively kill tumor cells. Molecular Therapy 21 (8) : 1621-1630. ScholarBank@NUS Repository.
Abstract: Intravenously injected neural stem cells (NSCs) can infiltrate both primary and metastatic tumor sites; thus, they are attractive tumor-targeting vehicles for delivering anticancer agents. However, because the systemic distribution of the injected NSCs involves normal organs and might induce off-target actions leading to unintended side effects, clinical applications of this approach is impeded. Given that the vesicular stomatitis virus glycoprotein (VSV-G) can promote the formation of multinucleated syncytia to kill cells in a pH-dependent manner, we engineered a pH sensor of VSV-G and generated a novel VSV-G mutant that efficiently promotes syncytium formation at the tumor extracellular pH (pH e) but not at pH 7.4. Using transduced NSCs derived from induced pluripotent stem cells (iPSCs), the VSV-G mutant was delivered into mice with metastatic breast cancers in the lung through tail vein injection. Compared with the conventional stem cell-based gene therapy that uses the herpes simplex virus thymidine kinase (HSVtk) suicide gene, this treatment did not display toxicity to normal non-targeted organs while retaining therapeutic effects in tumor-bearing organs. Our findings demonstrate the effectiveness of a new approach for achieving tumor-selective killing effects following systemic stem cell administration. Its potential in stem cell-based gene therapy for metastatic cancer is worthy of further exploration. © The American Society of Gene & Cell Therapy.
Source Title: Molecular Therapy
ISSN: 15250016
DOI: 10.1038/mt.2013.123
Appears in Collections:Staff Publications

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