Please use this identifier to cite or link to this item:
https://doi.org/10.1038/mt.2013.123
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. https://doi.org/10.1038/mt.2013.123 | 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 | URI: | http://scholarbank.nus.edu.sg/handle/10635/101808 | ISSN: | 15250016 | DOI: | 10.1038/mt.2013.123 |
Appears in Collections: | Staff Publications |
Show full item record
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.