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Targeting human glioma cells using HSV-1 amplicon peptide display vector

Gene Therapy volume 17, pages 250–260 (2010)Cite this article

Abstract

Targeting cell infection using herpes simplex virus type 1 (HSV-1) vectors is a complicated issue as the process involves multiple interactions of viral envelope glycoproteins and cellular host surface proteins. In this study, we have inserted a human glioma-specific peptide sequence (denoted as MG11) into a peptide display HSV-1 amplicon vector replacing the heparan sulfate-binding domain of glycoprotein C (gC). The modified MG11:gC envelope recombinant vectors were subsequently packaged into virions in the presence of helper virus deleted for gC. Our results showed that the tropism of these HSV-1 recombinant virions was increased for human glioma cells in culture as compared with wild-type virions. The binding of these recombinant virions could also be blocked effectively by pre-incubating the cells with the glioma-specific peptide, indicating that MG11 peptide and the recombinant virions competed for the same or similar receptor-binding sites on the cell surface of human glioma cells. Furthermore, preferential homing of these virions was shown in xenograft glioma mouse model following intravascular delivery. Taken together, these results validated the hypothesis that HSV-1 binding to cells can be redirected to human gliomas through the incorporation of MG11 peptide sequence to the virions.

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Acknowledgements

We express our gratitude to Breakefield XO (Departments of Neurology and Radiology, Harvard Medical School) for her valuable advices and assistance in proofreading. Special thanks to Brandt CR (UW-Madison School of Medicine and Public Health) for providing us with the gC-deleted helper viruses, Spear MA (University of California, San Diego) for providing pCONGA4 amplicon vectors and Khor HY for her assistance with the propagation of viruses. This work was supported by grants from the Agency for Science, Technology and Research (A*STAR) and SingHealth Foundation.

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Author notes

  1. I A W Ho and L Miao: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Cellular and Molecular Research, Laboratory of Cancer Gene Therapy, Humprey Oei Institute of Cancer Research, National Cancer Centre, Singapore

    I A W Ho, L Miao, K C Sia & P Y P Lam

  2. CHORI-Research, Children's Hospital Oakland Research Institute, Oakland, CA, USA

    G Y Wang

  3. Division of Cellular and Molecular Research, Bek Chai Heah Laboratory of Cancer Genomics, Humprey Oei Institute of Cancer Research, National Cancer Centre, Singapore

    K M Hui

  4. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

    P Y P Lam

  5. Cancer & Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore

    P Y P Lam

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  1. I A W Ho
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Correspondence to P Y P Lam.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Ho, I., Miao, L., Sia, K. et al. Targeting human glioma cells using HSV-1 amplicon peptide display vector. Gene Ther 17, 250–260 (2010). https://doi.org/10.1038/gt.2009.128

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