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Transcriptional retargeting of herpes simplex virus for cell-specific replication to control cancer

  • Weihua Lou
  • Fang Ji
  • Jianing Fu
  • Zhiqiang Han
  • Wen Di
  • Ning Zhang
Review – Cancer Research
  • 320 Downloads

Abstract

Introduction

Oncolytic virotherapy has emerged as a novel frontier in the treatment of cancer. Among the viruses that entered clinical trials are the oncolytic herpes simplex virus-1 (HSV-1). Current oncolytic HSV-1 approved for clinical practice, and those in clinical trials are attenuated viruses, often deleted in the neurovirulence gene γ134.5, and in additional genes, which may result in a much more attenuated virus with reduced replication efficiency. Therefore, the transcriptional retargeting strategy by modifying the regulator elements flanking essential viral genes to achieve tumor-specific replication while maintaining as much of the viral genome has been representing alternative promising oncolytic virotherapy modality.

Materials and methods

In this communication, we aimed to review extensive studies on transcriptional retargeting strategy with HSV-1 genome engineered on immediate–early ICP4 gene, late γ134.5 gene or early ICP6 gene as well as multiple-regulated oncolytic HSV1 through combining transcriptional retargeting and translational control. Design modality based on differential cellular background, advantage, and potential clinic limitation of the innovative oncolytic HSV-1 was described, and prospective and challenge of transcriptional retargeting strategy were collectively summarized.

Conclusion

Transcriptional retargeting strategy holds great promise in retaining tumor specificity as well as full replication capacity of oncolytic virus in the target cell as urgently required by clinical trials. Future efforts should be aimed toward the development of multiple-component targeted oncolytic virus such as combing the transcriptional retargeting strategy and genetically attenuated modulation or post-transcriptional control that will be the most effective at generating truly tumor selective vectors.

Keywords

Oncolytic virotherapy Herpes simplex virus-1 (HSV-1) Conditionally replicative Transcriptional control Tumor selective promoter 

Notes

Acknowledgements

We gratefully thank Dr. Robert S. Coffin (major researcher participating in construction of T-VEC and the management of T-VEC clinical trial) for his helpful review of the manuscript. This study was funded by the Natural Science Foundation of Science and Technology Commission of Shanghai Municipality (No. 16ZR1420000), China.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical statements

This article does not contain any studies with human participations or animals performed by any of the authors.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Obstetrics and Gynecology, Ren Ji Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiChina
  2. 2.Shanghai Key Laboratory of Gynecologic OncologyShanghaiChina
  3. 3.Columbia Center for Translational ImmunologyColumbia University Medical CenterNew YorkUSA
  4. 4.Viri Biotechnology Company LimitedZhengzhouChina

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