Efficient transduction of neurons using Ross River glycoprotein-pseudotyped lentiviral vectors

Gene Therapy
Johan JakobssonCecilia Lundberg

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.

References

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Citations

Oct 18, 2011·Neurobiology of Disease·Thomas B LentzR Jude Samulski
Apr 5, 2011·Experimental Neurology·Fredric P Manfredsson, Ronald J Mandel
Dec 9, 2008·Journal of Neuroscience Methods·Maja-Theresa DieterlenJohannes Schwarz
Nov 27, 2007·Advanced Drug Delivery Reviews·Yi LaiThomas Linn
Jan 1, 2013·Genes·Troels T Nielsen, Jørgen E Nielsen
Sep 6, 2017·Human Gene Therapy Methods·Alok V Joglekar, Salemiz Sandoval
Dec 15, 2020·Biomaterials Science·João ConniotJoão Conde

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