¹Department of Experimental Medical Research, Section for Neuroscience, Wallenberg Neuroscience Center, Lund University, Lund, Sweden

Correspondence: Dr C Lundberg, Department of Experimental Medical Research, Section for Neuroscience, Wallenberg Neuroscience Center, Lund University, BMC, A11, Lund 221 84, Sweden. E-mail: cecilia.lundberg@med.lu.se

Received 24 August 2005; Revised 13 October 2005; Accepted 1 November 2005; Published online 2 March 2006.

Abstract

Lentiviral vectors are promising tools for CNS gene transfer since they efficiently transduce the cells of the nervous system in vivo. In this study, we have investigated the transduction efficiency of lentiviral vectors pseudotyped with Ross River virus glycoprotein (RRV-G) (RRV-G-pseudotyped lentiviral vectors (RRV-LV)). The RRV is an alphavirus with an extremely broad host range, including the cells of the central nervous system. Previous studies have shown that lentiviral vectors can be efficiently pseudotyped with this envelope protein and have demonstrated promising features of such vectors, including the possibility to establish stable producer cell lines. After injection of RRV-LV expressing green fluorescent protein into different structures in the rat brain we found efficient transduction of both neurons and glial cells. By using two cell-type-specific promoters, neuron-specific enolase and human glial fibrillary acidic protein, we demonstrated cell-specific transgene expression in the desired cell type. Ross River virus glycoprotein-pseudotyped lentiviral vectors also transduced human neural progenitor cells in vitro, showing that receptors for the RRV-G are present on human neural cells.