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Type I interferon response against viral and non‐viral gene transfer in human tumor and primary cell lines
Author(s) -
Rautsi Outi,
Lehmusvaara Saara,
Salonen Tuula,
Häkkinen Katja,
Sillanpää Maarit,
Hakkarainen Tanja,
Heikkinen Sami,
Vähäkangas Elisa,
YläHerttuala Seppo,
Hinkkanen Ari,
Julkunen Ilkka,
Wahlfors Jarmo,
Pellinen Riikka
Publication year - 2007
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.997
Subject(s) - biology , interferon , transfection , virology , semliki forest virus , gene , viral vector , gene expression , virus , interferon type i , rna , cell culture , microbiology and biotechnology , genetics , recombinant dna
Background Type I interferon (IFN‐α/β) response is one of the major host defence mechanisms against viruses. Some recent reports suggest that IFNs may interfere with the efficacy of both non‐viral and virus‐vector‐mediated therapeutic gene transfer. Methods The type I IFN response upon different gene transfer methods in human tumor and primary cell lines was studied by analysing IFN‐β mRNA expression, secretion of type I IFNs and accumulation of IFN‐α/β‐induced MxA protein (myxovirus resistance protein A). Results Infection with avirulent Semliki Forest virus A7[74] induced MxA protein accumulation and increased the IFN‐β mRNA level, whereas none of the studied virus vectors (adenovirus, CRAd, lentivirus or AAV) induced IFN response. However, plasmid DNA induced the accumulation of MxA protein when transfected with several commercial transfection reagents. RNA transfection appeared to be an efficient inducer of type I IFN response: replicating alphaviral RNA, eukaryotic total RNA, or mRNA all induced both MxA protein accumulation and IFN‐β expression. siRNA transfection failed to induce MxA response. Conclusions The non‐viral gene transfer methods have gained more interest in recent years due to their better safety profiles when compared to their viral counterparts. However, the efficiency of non‐viral gene transfer is well below those reached by viral vector systems. The type I interferon response induced by non‐viral methods may in part contribute to this inefficiency, while most currently used viral gene transfer vectors fail to induce or are able to suppress type I IFN response. Copyright © 2006 John Wiley & Sons, Ltd.