Abstract
New drug-eluting stent (DES) methods have recently been demonstrated to improve outcomes of intravascular interventions. A novel technique is the design of gene-silencing stents that elute specific small-interfering RNAs (siRNAs) for better vascular wall regeneration. Although siRNAs used to alter gene expression have surpassed expectations in in vitro experiments, the functional and local delivery of siRNAs is still the major obstacle for the in vivo application of RNA interference. In this preliminary in vitro study we investigated a surface-immobilized siRNA delivery technique that would be readily adaptable for local intravascular applications in vivo. The transfection potency of gelatin coatings consisting of a specific siRNA complexed with polyethylenimine (PEI) was examined in primary human endothelial cells by flow cytometry and quantitative real-time polymerase chain reaction. Several media conditions, such as the presence or absence of serum during cultivation, were investigated. Furthermore, different siRNA and PEI amounts, as well as nitrogen/phosphate ratios, were tested for their transfection efficiency. Gelatin coatings consisting of PEI and siRNA against an exemplary endothelial adhesion molecule receptor achieved a significant knockdown of around 70%. The transfection efficiency of the coatings was not influenced by the presence of serum. The results of this preliminary study support the expectation that this novel coating may be favorable for local in vivo gene silencing (for example, when immobilized on stents or balloons for percutanous transluminal coronary angioplasty). However, further animal experiments are needed to confirm the translation into clinical practice. This intriguing technology leads the way to more sophisticated and individualized coatings for the post-DES era, toward silencing of genes involved in the pathway of intimal hyperplasia.
Highlights
During recent decades considerable advances have been achieved in intravascular interventions for the treatment of arterial disease
A novel technique may arise through the design of “gene silencing stents” that elute specific small-interfering RNAs to improve vascular wall regeneration by silencing of genes involved in the pathway of intimal hyperplasia development
There was no significant difference in the knockdown of the E-selectin receptor in cells that were cultivated for 4 h without serum after their adhesion to the well plates, compared with cells growing continually in the presence of serum
Summary
During recent decades considerable advances have been achieved in intravascular interventions for the treatment of arterial disease. Results of several clinical studies indicate that the ideal stent is not yet available, and industries as well as the scientific community continue to work hard on the development of more sophisticated solutions for the post-DES era. Gene silencing by RNA interference (RNAi) has become established as a powerful technique for the down-regulation of any target gene of interest in basic research, drug discovery, and therapeutic applications [3,4,5,6]. With this technique, optimized small interfering RNAs (siRNAs) are incorporated into the RNA-
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