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RETRACTED ARTICLE: Targeted suicide gene therapy for glioma using human embryonic stem cell-derived neural stem cells genetically modified by baculoviral vectors

Gene Therapy volume 19, pages 189–200 (2012)Cite this article

A Retraction to this article was published on 28 February 2020

Abstract

Tumor-tropic neural stem cells (NSCs) can be used in the Trojan horse approach as cellular vehicles for targeted delivery of therapeutic agents to distant tumor sites. To realize this cancer therapy potential, it is important to have a renewable source to generate large quantities of uniform human NSCs. Here, we reported that NSCs derived from HES1 human embryonic stem cell line were capable of migrating into intracranial glioma xenografts after systemic injection or after intracranial injection at a site distant from the tumor. To test whether the HES1-derived NSCs can be used for cancer gene therapy, we used a baculoviral vector to introduce the herpes simplex virus thymidine kinase suicide gene into the cells and demonstrated that baculovirus-mediated transgene expression may last for at least 3 weeks in NSCs. After being injected into the cerebral hemisphere opposite the tumor site and in the presence of ganciclovir, NSCs expressing the suicide gene were able to inhibit the growth of human glioma xenografts and prolong survival of tumor-bearing mice. Our findings suggest that human embryonic stem cells could potentially serve as a clinically viable source for production of cellular vehicles suitable for targeted anticancer gene therapy.

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Acknowledgements

This work was supported by Institute of Bioengineering and Nanotechnology, Biomedical Research Council, Agency for Science, Technology and Research (A*STAR) in Singapore and a grant from National Medical Research Council in Singapore (NMRC/1203/2009).

Author information

Authors and Affiliations

  1. Drug and Gene Delivery, Institute of Bioengineering and Nanotechnology, Singapore, Singapore

    Y Zhao, D H Lam, J Lin & S Wang

  2. Department of Biological Sciences, National University of Singapore, Singapore, Singapore

    J Yang & S Wang

  3. Department of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore

    C K Tham

  4. Department of Neurosurgery, National Neuroscience Institute, Singapore, Singapore

    W H Ng

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Correspondence to S Wang.

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Additional information

The editor has retracted this article following an investigation by Agency for Science, Technology and Research (A*STAR), Institute of Bioengineering and Nanotechnology, Singapore, which found evidence of fabricated animal survival data presented in Figure 7C in the article to make the results statistically significant. D H Lam, J Yang, J Lin, C K Tham, W H Ng & S Wang agree to this retraction. Y Zhao has agreed to this retraction but not to the wording of this retraction notice.

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Zhao, Y., Lam, D., Yang, J. et al. RETRACTED ARTICLE: Targeted suicide gene therapy for glioma using human embryonic stem cell-derived neural stem cells genetically modified by baculoviral vectors. Gene Ther 19, 189–200 (2012). https://doi.org/10.1038/gt.2011.82

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