Journal of Antivirals & Antiretrovirals
Open Access
ISSN: 1948-5964
ISSN: 1948-5964
Michael Fassler, Itai Weissberg, Ehud Sharony, Nitzan Levi, Alon Monsonego, Alon Friedman and Ran Taube
Posters: JAA
In a complex tissue of the central nervous system (CNS), cell cross-talk is essential to preserve normal functions. Current tools for dissecting the molecular mechanisms that mediate cellcell interactions within the brain include molecular genetics, imaging and use of transgenic animals. However, these are technically challenging, time consuming and diffi cult to control. In this study we report the establishment and validation of a lentiviral-mediated gene-targeting platform to specifi c cells in the CNS. It combines unique features of self-inactivated lentiviruses that promote stable gene delivery into non-dividing cells and effi cient display of single-chain variable region human fragments (scFv) or soluble IgG on the surface of viral particles. In vitro, cells that express the receptor-binding domain of the SARS CoV spike glycoprotein were targeted by engineered sindbis pseudotyped lentiviruses that incorporate specifi c scFvFc attachment moieties. Additionally, in vitro targeted gene expression to primary astrocytes was also demonstrated, using engineered lentiviruses that incorporate Aquaporin 4 IgG. In vivo, lentiviral targeting of oligodentrocyes progenitor cells (OPCs) that express the chondroitin sulfate proteoglycan, NG2 was obtained using viral particles that display an anti NG2 IgG. We conclude that this genetic delivery tool can be used for specifi c targeting of several genes into diff erent cell populations. Moreover, it will enable effi cient fating and imaging studies during CNS development, as well as enhance the understanding of the molecular mechanisms that mediate cell communication in healthy and diseased brain. Importantly, it can open a window for the development of novel strategies for treating CNS pathologies.
Michael Fassler received his M.Sc degree in 2010 from the Department of Virology, Faculty of Health Science, Ben-Gurion University of the Negev, Beer-Sheva, Israel. He is currently completing his Ph.D. degree in the Department of Virology, Faculty of Health Science, and in the Department of Physiology and Neurobilogy, Ben-Gurion University of the Negev. His research work involves developing a gene-targeting platform using lentiviruses that can mediate specifi c gene delivery into cells of the CNS.