Toxicogenomics of drug delivery systems: Exploiting delivery system-induced changes in target gene expression to enhance siRNA activity

被引：98

作者：

Hollins, Andrew J.

Omidi, Yadollah

Benter, Ibrahim F.

Akhtar, Saghir

机构：

[1] Cardiff Univ, Sch Pharm, Ctr Genome Based Therapeut, Cardiff CF10 3XF, S Glam, Wales

[2] Kuwait Univ, Fac Med, Dept Pharmacol & Toxicol, Safat, Kuwait

[3] SA Pharma, Sutton Cornfield B73 5NP, W Midlands, England

来源：

JOURNAL OF DRUG TARGETING | 2007年 / 15卷 / 01期

基金：

英国生物技术与生命科学研究理事会;

关键词：

siRNAs; drug delivery systems; dendrimer; epidermal growth factor receptor; gene expression; microarray;

D O I：

10.1080/10611860601151860

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：83 / 88

页数：6

共 16 条

[1] Gene silencing nucleic acids designed by scanning arrays: Anti-EGFR activity of siRNA, ribozyme and DNA enzymes targeting a single hybridization-accessible region using the same delivery system [J].