PDF(Pubmed)
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.
摘要：
利用慢病毒载体(LV)的基因递送系统需要高转导效率以成功应用于人类基因治疗。假型可以扩大病毒嗜性，扩大LV的使用范围。虽然水泡性口炎病毒G（VSV-G）单假型LV通常使用，双重假型化的使用频率较低，因为它增加了复杂性。在这项研究中,我们研究了与VSV-G和仙台病毒血凝素-神经氨酸酶（SeV-HN）糖蛋白的表型混合的异源双重假型LV的潜力，称为V/HN-LV。我们的发现表明V/HN-LV在小鼠的各种细胞系中的转导效率显著提高,食蟹猴,和人类与单独使用VSV-G的假型LV相比。值得注意的是,V/HN-LV在人体细胞中显示出更高的转导效率，包括造血干细胞.野生型SeV-HN有效掺入V/HN-LV取决于VSV-G。SeV-HN从VSV-G中去除唾液酸，VSV-G的去唾液酸化增加了V/HN-LV的感染性。此外，V/HN-LV获得了识别唾液酸的能力，特别是宿主细胞上的N-乙酰神经氨酸，增强LV感染性。总的来说,VSV-G和SeV-HN协同提高LV转导效率，拓宽其取向，表明它们在基因传递中的潜在用途。
