A Replication-Competent Retroviral Vector Expressing the HERV-W Envelope Glycoprotein is a Potential Tool for Cancer Gene Therapy

• Published in: Journal of microbiology and biotechnology Vol. 34; no. 2; pp. 280 - 288
• Main Authors: Kang, Byoung Kwon, Jung, Yong-Tae
• Format: Journal Article
• Language: English
• Published: Korea (South) 한국미생물·생명공학회 01.02.2024
• Subjects: Endogenous Retroviruses - genetics; Endogenous Retroviruses - metabolism; Genes, Neoplasm; Genetic Vectors - genetics; HEK293 Cells; Humans; Membrane Glycoproteins - genetics; Neoplasms - genetics; Neoplasms - therapy; Viral Envelope Proteins - genetics; 생물학; FMG; RCR vector; syncytium; s-RCR vector; HERV-W env; Cancer gene therapy
• ISSN: 1017-7825; 1738-8872
• DOI: 10.4014/jmb.2309.09022

The fusogenic membrane glycoprotein (FMG) derived from the human endogenous retrovirus-W (HERV-W) exhibits fusogenic properties, making it a promising candidate for cancer gene therapy. When cells are transfected with HERV-W FMG, they can fuse with neighboring cells expressing the receptor, resulting in the formation of syncytia. These syncytia eventually undergo cell death within a few days. In addition, it has been observed that an HERV-W mutant, which is truncated after amino acid 483, displays increased fusogenicity compared to the wild-type HERV-W . In this study, we observed syncytium formation upon transfection of HeLa and TE671 human cancer cells with plasmids containing the HERV-W 483 gene. To explore the potential of a semi-replication-competent retroviral (s-RCR) vector encoding HERV-W 483 for FMG-mediated cancer gene therapy, we developed two replication-defective retroviral vectors: a vector encoding HERV-W 483 (MoMLV-HERV-W 483) and an vector encoding VSV-G (pCLXSN-VSV-G-EGFP). When MoMLV-HERV-W 483 and pCLXSN-VSV-G-EGFP were co-transfected into HEK293T cells to produce the s-RCR vector, gradual syncytium formation was observed. However, the titers of the s-RCR virus remained consistently low. To enhance gene transfer efficiency, we constructed an RCR vector encoding HERV-W 483 (MoMLV-10A1-HERV-W 483), which demonstrated replication ability in HEK293T cells. Infection of A549 and HT1080 human cancer cell lines with this RCR vector induced syncytium formation and subsequent cell death. Consequently, both the s-RCR vector and RCR encoding HERV-W 483 hold promise as valuable tools for cancer gene therapy.