Modulating Polymer-siRNA Binding Does Not Promote Polyplex-Mediated Silencing
Modulating Polymer-siRNA Binding Does Not Promote Polyplex-Mediated Silencing
复制标题
调节聚合物-siRNA 结合不会促进 Polyplex 介导的沉默
DOI：
10.1089/nat.2020.0857
复制
发表时间：
2021
影响因子：
4
通讯作者：
Walton, S. Patrick
中科院分区：
文献类型：
--
作者：
Splichal, R. Chauncey;Gredell, Joseph A.;Vogel, Erin B.;Malefyt, Amanda;Comiskey, Georgina;Smith, Milton R.;Chan, Christina;Walton, S. Patrick
小干扰RNA（siRNA）的递送载体的开发仍然是广泛临床应用的瓶颈。阳离子聚合物代表一类重要的潜在递送载体。在这项研究中，我们使用炔-叠氮点击化学合成了各种阳离子聚（炔丙基乙交酯）骨架聚合物结合和交付siRNA。我们证明了通过改变超过三个数量级的结合强度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。我们的聚合物有效地递送siRNA，没有可检测到的细胞毒性。尽管siRNA的积累水平与商业试剂相当，但我们没有观察到靶蛋白的沉默。我们的研究结果对未来siRNA运载工具设计的影响进行了讨论。
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.