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This galley proof is being listed electronically before publishing the final manuscript (It's not final version).

Split genome-based retroviral replicating vectors achieve efficient gene delivery and therapeutic effect in a human glioblastoma xenograft model
Moonkyung Kang1 (Reserach worker), Ayoung Song2 (Graduate student), Jiyoung Kim1 (Research worker), Se Hun Kang3 (Research worker), Sang-Jin Lee3 (Research worker), Yeon-Soo Kim 1,* (Professor)
1Graduate School of New Drug Discovery & Development, Chungnam National University,
2Department of Biomedical Laboratory Science, Inje University,
3Research Institute and Hospital, National Cancer Center of Korea
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 gruops ) died within 45 days after tumor injection. In conclusion, these findings suggest 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.
Abstract, Accepted Manuscript(in press) [Submitted on September 5, 2022, Accepted on October 4, 2022]
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