title: Cell-specific RNA interference by peptide-inhibited-peptidase-activated siRNAs.
abstract: The use of chemically-synthesized short interfering RNAs (siRNAs) is the key method of choice to manipulate gene expression in mammalian cell cultures and in vivo. Several previous studies have aimed at inducing cell-specific RNA interference (RNAi) in order to use siRNA molecules as therapeutic reagents. Here, we used peptide-inhibited siRNAs that were activated after cleavage by cell-specific peptidases. We show that siRNAs with bound peptide at the antisense strand could be activated in target cells and were able to induce RNAi in a cell-specific manner. Green Fluorescent Protein (GFP) and Signal Transducer and Activator of Transcription (STAT)-3 gene expression were selectively reduced in a JEG-3 human choriocarcinoma cell line expressing the activating enzyme caspase-4, whereas the effect was absent in HEK cells which lacked the enzyme. In JEG-3 cells, reduction of STAT3 gene expression by conventional and peptide-inhibited siRNA led to a decrease in cell proliferation. This suggests that peptide-inhibited siRNAs provide improved cell specificity and offers new opportunities for their therapeutic use.
authors.affiliation: Placenta-Lab, Dept of Obstetrics, Friedrich-Schiller-University Jena, Bachstr 18, 07743 Jena, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Koehn
authors.forename: Hendrik W
authors.initials: HW
authors.lastname: Schaefer
authors.forename: Mirko
authors.initials: M
authors.lastname: Ludwig
authors.forename: Natja
authors.initials: N
authors.lastname: Haag
authors.forename: Ulrich S
authors.initials: US
authors.lastname: Schubert
authors.forename: Lydia
authors.initials: L
authors.lastname: Seyfarth
authors.forename: Diana
authors.initials: D
authors.lastname: Imhof
authors.forename: Udo R
authors.initials: UR
authors.lastname: Markert
authors.forename: Tobias G
authors.initials: TG
authors.lastname: Poehlmann