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Viruses ; 16(6)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38932120

RESUMEN

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.


Asunto(s)
Vectores Genéticos , Proteína HN , Lentivirus , Virus Sendai , Transducción Genética , Proteínas del Envoltorio Viral , Animales , Humanos , Vectores Genéticos/genética , Lentivirus/genética , Virus Sendai/genética , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/metabolismo , Ratones , Proteína HN/genética , Proteína HN/metabolismo , Línea Celular , Macaca fascicularis , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Tropismo Viral , Células HEK293 , Técnicas de Transferencia de Gen , Terapia Genética/métodos
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