Designed guanidinium-rich amphipathic oligocarbonate molecular transporters complex, deliver and release siRNA in cells
Designed guanidinium-rich amphipathic oligocarbonate molecular transporters complex, deliver and release siRNA in cells
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DOI：
10.1073/pnas.1211361109
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发表时间：
2012-08-14
影响因子：
11.1
通讯作者：
Wender, Paul A.
中科院分区：
文献类型：
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作者：
Geihe, Erika I.;Cooley, Christina B.;Wender, Paul A.
寡核苷酸的聚阴离子性质及其酶促降解对siRNA在研究和治疗中的使用提出了挑战;其中最值得注意的是临床相关的递送到细胞中。为了解决这个问题，我们设计并合成了一类新型富含胍的两亲性低聚碳酸酯的第一批成员，它们在细胞中非共价复合、递送和释放siRNA，从而在体外强烈抑制靶蛋白合成，如使用所确定的那样双报告系统。用于合成这些共低聚物的有机催化低聚是步骤经济的并且广泛可调的，提供了一种异常快速的策略来探索化学空间以在各种应用中进行最佳siRNA递送。这种方法的速度和多功能性以及所设计试剂的生物降解性使其成为生物工具开发、成像、诊断和治疗应用的有吸引力的策略。
The polyanionic nature of oligonucleotides and their enzymatic degradation present challenges for the use of siRNA in research and therapy; among the most notable of these is clinically relevant delivery into cells. To address this problem, we designed and synthesized the first members of a new class of guanidinium-rich amphipathic oligocarbonates that noncovalently complex, deliver, and release siRNA in cells, resulting in robust knockdown of target protein synthesis in vitro as determined using a dual-reporter system. The organocatalytic oligomerization used to synthesize these co-oligomers is step-economical and broadly tunable, affording an exceptionally quick strategy to explore chemical space for optimal siRNA delivery in varied applications. The speed and versatility of this approach and the biodegradability of the designed agents make this an attractive strategy for biological tool development, imaging, diagnostics, and therapeutic applications.