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The mutant Sindbis virus E2 glycoprotein is an engineered viral envelope protein used to pseudotype lentiviral vectors for highly specific gene delivery (Yang et al., 2008, Nature Biotechnology). While the wild-type Sindbis virus E2 protein exhibits broad cellular tropism, the mutant version (often referred to as SVGmu) contains specific amino acid substitutions that eliminate its ability to bind heparan sulfate proteoglycans and redirect it to the DC-SIGN (CD209) receptor (Yang et al., 2008). This receptor is predominantly expressed on dendritic cells, allowing lentiviral vectors to selectively transduce these professional antigen-presenting cells in vivo (Pollack et al., 2017, Oncoimmunology). This targeting mechanism is the core of the ZVex platform, which has been utilized in clinical-stage cancer vaccines such as LV305 to deliver the NY-ESO-1 antigen directly to the immune system (Homet Moreno et al., 2016, Journal for ImmunoTherapy of Cancer). By facilitating the direct transduction of dendritic cells, the mutant E2 glycoprotein helps generate potent, antigen-specific CD8+ T-cell responses while minimizing off-target effects in non-immune tissues. This technology represents a significant advancement in immunotherapy, offering a way to induce robust immune responses without the need for ex vivo cell manipulation (Ter Meulen et al., 2015, Immune Design).
Pseudotyping of lentiviral vectors to enable specific transduction of dendritic cells via binding to DC-SIGN (CD209)
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