Journal
JOURNAL OF DRUG TARGETING
Volume 15, Issue 1, Pages 83-88Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10611860601151860
Keywords
siRNAs; drug delivery systems; dendrimer; epidermal growth factor receptor; gene expression; microarray
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Synthetic siRNAs are typically formulated with drug delivery systems (DDS) that improve cellular uptake for optimal gene silencing activity. Here, we show that two PAMAM dendrimer DDS, differing only in their structural architecture, elicit many different gene expression changes in human cells including opposing effects on the expression of epidermal growth factor receptor (EGFR), a gene targeted for silencing by siRNA. Despite providing similar improvements in siRNA uptake, these two formulations led to a similar to 10-fold variation in anti-EGFR siRNA activity. These data show that gene expression changes induced by DDS, separate from their ability to enhance cell uptake, determine 'apparent' siRNA potency and thus offer the possibility of tailoring delivery system-siRNA combinations for additive or synergistic effects on gene silencing.
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