RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo

By confocal microscopy we studied the halflife/intracellular fate of fluorescently labeled JetPEI upon transfection of cells with PEI/small interfering RNAs complexes

B Urban-Klein; S Werth; S Abuharbeid; F Czubayko; A Aigner

2004

Scholarcy highlights

  • ‘crude’ small interfering RNAs might work under certain circumstances, a system stabilizing siRNAs and enhancing their delivery into cells would clearly offer advantages
  • RNA interference is induced by small 21–25 nt double-stranded small interfering RNAs, which become incorporated into the RNA-induced silencing complex and serve as a guide for endonucleolytic cleavage of the complementary target mRNA
  • It is clear that the efficient delivery of intact siRNAs will play a rate-limiting role in any mammalian gene therapy application and has so far widely limited in vivo applications of RNAi
  • While SKOV-3 cells treated with a PEI-complexed nonspecific control siRNA showed high numbers of large colonies 490 mm, a single treatment with HER-2-specific, PEI-complexed siRNAs led to a B50% reduction of colony formation
  • SKOV-3 cells were subcutaneously injected into the flanks of athymic nude mice, and when tumors reached a size of B10 mm, animals were treated every 2–3 days with 0.6 nmol PEI-complexed HER-2 siRNAs or a PEIcomplexed unrelated siRNA as negative control
  • To test if HER-2-specific siRNAs exert an inhibitory effect on tumor growth without prior PEI complexation, the experiment was repeated with i.p. injection of naked compared to PEIcomplexed HER-2 siRNA
  • The effects observed in our in vivo tumor model upon targeting of the HER-2 receptor proves that PEI complexation of small interfering RNAs offers an avenue for the development of highly efficient, specific and safe agents for therapeutical applications

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