The development of delivery vehicles for small interfering RNAs (siRNAs) remains a bottleneck to widespread clinical use. Cationic polymers represent an important class of potential delivery vehicles. In this study, we used alkyne-azide click chemistry to synthesize a variety of cationic poly(propargyl glycolide) backbone polymers to bind and deliver siRNAs. We demonstrated control over the binding interactions of these polymers and siRNAs by varying binding strength by more than three orders of magnitude. Binding strength was found to meet or exceed that of commercially available transfection agents. Our polymers effectively delivered siRNAs with no detectable cytotoxicity. Despite accumulation of siRNAs at levels comparable with commercial reagents, we did not observe silencing of the targeted protein. The implications of our results for future siRNA delivery vehicle design are discussed.

中文翻译：

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调节聚合物-siRNA 结合不会促进 Polyplex 介导的沉默

小干扰 RNA (siRNA) 递送载体的开发仍然是广泛临床应用的瓶颈。阳离子聚合物代表了一类重要的潜在递送载体。在这项研究中，我们使用炔烃-叠氮化物点击化学来合成各种阳离子聚（炔丙乙交酯）主链聚合物来结合和递送 siRNA。我们证明了通过将结合强度改变三个以上数量级来控制这些聚合物和 siRNA 的结合相互作用。发现结合强度达到或超过市售转染剂的结合强度。我们的聚合物可有效递送 siRNA，且未检测到细胞毒性。尽管 siRNA 的积累水平与商业试剂相当，但我们没有观察到目标蛋白的沉默。讨论了我们的结果对未来 siRNA 递送载体设计的影响。