LVs displaying endothelial-specific envelopes specifically target LSECs after systemic injection. This endothelial specificity was achieved using a chimeric measles virus envelope (CD105-scFv-H_mut) composed of an scFv specific for CD105 genetically linked to a mutated measles virus hemagglutinin H protein. The pseudotyped LV particles also displayed a mutated fusogenic measles virus F protein on their surface to mediate entry into the target cells. The exquisite endothelial specificity of these CD105-specific LVs was confirmed in tumor-derived endothelium and in human veins and arteries ex vivo. Professional illustration by Debra T. Dartez.