Induction of interferon synthesis and activation of interferon-stimulated genes by liposomal transfection reagents

Liposome-mediated transfection is a widely used technique for the introduct ion of exogenous DNA into mammalian cells. We observed a significant induct ion of endogenous interferon (IFN)-stimulated genes (ISGs) in cells treated with the liposomal reagents, lipofectamine and DOSPER, in the absence of D NA, Liposome treatment induced expression of reporter constructs driven by IFN-responsive promoter elements, demonstrating a generalized effect on ISG expression. The kinetics of ISG induction were markedly delayed in respons e to liposome as compared with IFN or double-stranded RNA. ISG induction co uld be transferred to naive cells with conditioned medium from liposome-tre ated cells, suggesting that a secreted factor was responsible for this acti vity. A cell line defective in IFN signaling was refractory to liposome-ind uced ISC expression, indicating a role for IFN in this induction, Indeed, l iposome treatment directly induced IFN-beta gene expression and, thus, repr esents a novel IFN inducer. IFN induction by liposomal reagents and its pot ential effects on transgene expression should be considered in the choice o f transfection reagent, The ability of liposomal gene delivery reagents to induce IFN synthesis in the host may prove useful in gene therapy approache s to viral and neoplastic diseases.