2010
DOI: 10.1186/1743-422x-7-35
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Targeting lentiviral vector to specific cell types through surface displayed single chain antibody and fusogenic molecule

Abstract: BackgroundViral delivery remains one of the most commonly used techniques today in the field of gene therapy. However, one of the remaining hurdles is the off-targeting effect of viral delivery. To overcome this obstacle, we recently developed a method to incorporate an antibody and a fusogenic molecule (FM) as two distinct molecules into the lentiviral surface. In this report, we expand this strategy to utilize a single chain antibody (SCAb) for targeted transduction.ResultsTwo versions of the SCAb were gener… Show more

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Cited by 19 publications
(14 citation statements)
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“…Although these additional mutations (AGM and SGN) were originally identified from Sindbis viruses propagated in cholesterol-depleted cells and viruses carrying these mutations were believed to be less dependent on cholesterol for fusion, we speculate that these FM molecules might also have different responsiveness to the endosomal pH, with SGN being the most responsive and fusion-active. Our reported vector–liposome fusion assay actually supports this speculation, and SGN was found to be the most pH-sensitive fusogen (Lei et al, 2010). Nevertheless, the reduction in transduction efficiency by the endosomal neutralization assay and the variations in transduction efficiencies among the different FM molecules provide sufficient evidence that endocytosis and endosomal trafficking must also be involved in the transduction process.…”
Section: Discussionsupporting
confidence: 66%
“…Although these additional mutations (AGM and SGN) were originally identified from Sindbis viruses propagated in cholesterol-depleted cells and viruses carrying these mutations were believed to be less dependent on cholesterol for fusion, we speculate that these FM molecules might also have different responsiveness to the endosomal pH, with SGN being the most responsive and fusion-active. Our reported vector–liposome fusion assay actually supports this speculation, and SGN was found to be the most pH-sensitive fusogen (Lei et al, 2010). Nevertheless, the reduction in transduction efficiency by the endosomal neutralization assay and the variations in transduction efficiencies among the different FM molecules provide sufficient evidence that endocytosis and endosomal trafficking must also be involved in the transduction process.…”
Section: Discussionsupporting
confidence: 66%
“…In the RPA platform, the phage-derived recombinase initially aggregates with the primers and forms nucleoprotein filaments. Then, the filaments scan the template DNA for homologous sequences and catalyze strand exchange at cognate sites [5]. The displaced strand is bound by a single-stranded DNA binding protein, and the primers then are extended by Bsu DNA polymerase.…”
Section: Introductionmentioning
confidence: 99%
“…For example, we used VSVG pseudotyped HIV-1 viruses characterized by a high tropism but the use of different envelope proteins, including those fused to singlechain antibodies (Lei et al, 2010), may allow the targeting of specific tissues and cell types. Whereas the use of loxP-containing lentiviruses in available Cre-expressing lines allows the use of our approach in applications as diverse as the Cre/loxP (or similar) system can provide (Fig.…”
Section: Lentiviruses Provide An Additional Powerful Resource To Manimentioning
confidence: 99%