BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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Split genome-based retroviral replicating vectors achieve efficient gene delivery and therapeutic effect in a human glioblastoma xenograft model

  • Moonkyung, Kang (Graduate School of New Drug Discovery and Development, Chungnam National University) ;
  • Ayoung, Song (Institue of Molecular Biology, Inje University) ;
  • Jiyoung, Kim (Graduate School of New Drug Discovery and Development, Chungnam National University) ;
  • Se Hun, Kang (Research Institute and Hospital, National Cancer Center of Korea) ;
  • Sang-Jin, Lee (Research Institute and Hospital, National Cancer Center of Korea) ;
  • Yeon-Soo, Kim (Graduate School of New Drug Discovery and Development, Chungnam National University)
  • 투고 : 2022.09.05
  • 심사 : 2022.10.04
  • 발행 : 2022.12.31
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초록

The murine leukemia virus-based semi-retroviral replicating vectors (MuLV-based sRRV) had been developed to improve safety and transgene capacity for cancer gene therapy. However, despite the apparent advantages of the sRRV, improvements in the in vivo transduction efficiency are still required to deliver therapeutic genes efficiently for clinical use. In this study, we established a gibbon ape leukemia virus (GaLV) envelope-pseudotyped semi-replication-competent retrovirus vector system (spRRV) which is composed of two transcomplementing replication-defective retroviral vectors termed MuLV-Gag-Pol and GaLV-Env. We found that the spRRV shows considerable improvement in efficiencies of gene transfer and spreading in both human glioblastoma cells and pre-established human glioblastoma mouse model compared with an sRRV system. When treated with ganciclovir after intratumoral injection of each vector system into pre-established U-87 MG glioblastomas, the group of mice injected with spRRV expressing the herpes simplex virus type 1-thymidine kinase (HSV1-tk) gene showed a survival rate of 100% for more than 150 days, but all control groups of mice (HSV1-tk/PBS-treated and GFP/GCV-treated groups) died within 45 days after tumor injection. In conclusion, these findings sug-gest that intratumoral delivery of the HSV1-tk gene by the spRRV system is worthy of development in clinical trials for the treatment of malignant solid tumors.

키워드

과제정보

This research was funded by grants from the Bio & Medical Technology Development Program of the National Research Foundation (NRF), funded by the Korean government (MSIT) (NRF-2018M3A9B5059544).

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