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  • The Dual-Pseudotyped Lentiviral Vector with VSV-G and Sendai Virus HN Enhances Infection Efficiency through the Synergistic Effect of the Envelope Proteins.

The Dual-Pseudotyped Lentiviral Vector with VSV-G and Sendai Virus HN Enhances Infection Efficiency through the Synergistic Effect of the Envelope Proteins.

Viruses (2024-06-27)
Bat-Erdene Jargalsaikhan, Masanaga Muto, Youngeun Been, Shoma Matsumoto, Eiichi Okamura, Tadanobu Takahashi, Yutaka Narimichi, Yuuki Kurebayashi, Hideyuki Takeuchi, Takashi Shinohara, Ryo Yamamoto, Masatsugu Ema
ABSTRACT

A gene delivery system utilizing lentiviral vectors (LVs) requires high transduction efficiency for successful application in human gene therapy. Pseudotyping allows viral tropism to be expanded, widening the usage of LVs. While vesicular stomatitis virus G (VSV-G) single-pseudotyped LVs are commonly used, dual-pseudotyping is less frequently employed because of its increased complexity. In this study, we examined the potential of phenotypically mixed heterologous dual-pseudotyped LVs with VSV-G and Sendai virus hemagglutinin-neuraminidase (SeV-HN) glycoproteins, termed V/HN-LV. Our findings demonstrated the significantly improved transduction efficiency of V/HN-LV in various cell lines of mice, cynomolgus monkeys, and humans compared with LV pseudotyped with VSV-G alone. Notably, V/HN-LV showed higher transduction efficiency in human cells, including hematopoietic stem cells. The efficient incorporation of wild-type SeV-HN into V/HN-LV depended on VSV-G. SeV-HN removed sialic acid from VSV-G, and the desialylation of VSV-G increased V/HN-LV infectivity. Furthermore, V/HN-LV acquired the ability to recognize sialic acid, particularly N-acetylneuraminic acid on the host cell, enhancing LV infectivity. Overall, VSV-G and SeV-HN synergistically improve LV transduction efficiency and broaden its tropism, indicating their potential use in gene delivery.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Tankyrase1/2 Inhibitor, XAV939, The Tankyrase1/2 Inhibitor, XAV939 controls the biological activity of Tankyrase1/2. This small molecule/inhibitor is primarily used for Phosphorylation & Dephosphorylation applications.
Sigma-Aldrich
Anti-VSV Glycoprotein antibody, Mouse monoclonal, clone P5D4, purified from hybridoma cell culture
Sigma-Aldrich
Sialyltransferase Inhibitor, 3Fax-Peracetyl Neu5Ac, The Sialyltransferase Inhibitor, 3Fax-Peracetyl Neu5Ac controls the biological activity of Sialyltransferase.