Methodology

Correction: RNA interference-mediated gene silencing in murine T cells: in vitro and in vivo validation of proinflammatory target genes

Tatjana C Gust¹ , Luisa Neubrandt¹ , Claudia Merz² , Khusru Asadullah² , Ulrich Zügel¹ and Arne von Bonin¹

¹  Common Mechanism Research, Global Drug Discovery, Bayer Schering Pharma AG, Muellerstrasse 178, 13342 Berlin, Germany

²  Target Discovery, Global Drug Discovery, Bayer Schering Pharma AG, Muellerstrasse 178, 13342 Berlin, Germany

author email corresponding author email

Cell Communication and Signaling 2008, 6:3doi:10.1186/1478-811X-6-3

Published:	6 August 2008

Abstract

T cells play a central role in many inflammatory diseases, hence the identification and validation of T cell-specific target genes will increase the understanding of T cell function in pathologic inflammatory situations. RNA interference (RNAi), with its ability to induce specific gene silencing in mammalian cells, represents a powerful technology to investigate and validate the function of pharmaceutical target genes in vitro and in vivo. The aim of the present study was to systematically explore RNAi-mediated gene-silencing of known T cell-specific model signaling molecules in primary murine T cells in vitro and in vivo. We demonstrate that siRNA delivery and subsequent silencing of T cell specific genes is substantially increased, if murine T cells were activated prior siRNA transfection. Silencing of ZAP70, p56Lck as well as PLC-γ1 protein expression resulted in impaired function of T cells in vitro. Furthermore, delayed type hypersensitivity (DTH) was ameliorated in vivo after adoptive transfer of ZAP70-silenced T cells. The combination of RNAi-mediated gene silencing and adoptive transfer of gene-silenced T cells, thus, may allow the identification and analysis of T cell-specific targets for therapeutic intervention. Additionally, this model system may represent an alternative to conventional time consuming and cost intensive gene targeting approaches.