ISY: Targeted Transduction via CD4 by a Lentiviral Vector Uses a Clathrin-Mediated Entry Pathway

We recently developed a novel targeting Sindbis virus envelope pseudotyped lentiviral vector, 2.2ZZ, which acquires specific transduction capacity by antibody conjugation and binding with specific antigens on the surface of targeted cells. Here we characterize the virological properties of this vector by examining its targeting to CD4 antigen. Our results show that entry is dependent on CD4 cell surface density and occurs via the clathrin-mediated endocytic pathway. These findings provide insight into the mechanism of infection by a new viral vector with combined properties of Sindbis virus and lentiviruses and infectivity conferred by monoclonal antibody-ligand interactions. Effective gene therapy in clinical settings will require the targeting of such therapies to specific tissues and organs while maintaining stable gene expression. We describe a novel tar-geting vector which acquires specific transduction capacity by antibody conjugation and binding to specific antigens on the surface of targeted cells. Our lab modified the fusion protein of Sindbis virus envelope, E2, by inserting an Fc-binding portion, the ZZ domain, of protein A (17, 19, 21). The lentiviral vecto