Cell-specific RNA interference by peptide-inhibited-peptidase-activated siRNAs.

Autor: Koehn S; Placenta-Lab, Dept of Obstetrics, Friedrich-Schiller-University Jena, Bachstr 18, 07743 Jena, Germany., Schaefer HW, Ludwig M, Haag N, Schubert US, Seyfarth L, Imhof D, Markert UR, Poehlmann TG
Jazyk: angličtina
Zdroj: Journal of RNAi and gene silencing : an international journal of RNA and gene targeting research [J RNAi Gene Silencing] 2010 Dec 31; Vol. 6 (2), pp. 422-30. Date of Electronic Publication: 2010 Dec 31.
Abstrakt: 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.
Databáze: MEDLINE