Reinhard Sören, Wagner Ernst
Pharmaceutical Biotechnology, Department of Pharmacy, Ludwig Maximilians University, 81377, Munich, Germany.
Nanosystems Initiative Munich (NIM), 80799, Munich, Germany.
Macromol Biosci. 2017 Jan;17(1). doi: 10.1002/mabi.201600152. Epub 2016 Jun 21.
RNA interference (RNAi) as a mechanism of gene regulation provides exciting opportunities for medical applications. Synthetic small interfering RNA (siRNA) triggers the knockdown of complementary mRNA sequences in a catalytic fashion and has to be delivered into the cytosol of the targeted cells. The design of adequate carrier systems to overcome multiple extracellular and intracellular roadblocks within the delivery process has utmost importance. Cationic polymers form polyplexes through electrostatic interaction with negatively charged nucleic acids and present a promising class of carriers. Issues of polycations regarding toxicity, heterogeneity, and polydispersity can be overcome by solid-phase-assisted synthesis of sequence-defined cationic oligomers. These medium-sized highly versatile nucleic acid carriers display low cytotoxicity and can be modified and tailored in multiple ways to meet specific requirements of nucleic acid binding, polyplex size, shielding, targeting, and intracellular release of the cargo. In this way, sequence-defined cationic oligomers can mimic the dynamic and bioresponsive behavior of viruses.
RNA干扰（RNAi）作为一种基因调控机制，为医学应用提供了令人兴奋的机会。合成小干扰RNA（siRNA）以催化方式引发互补mRNA序列的敲低，并且必须递送至靶细胞的细胞质中。设计合适的载体系统以克服递送过程中的多个细胞外和细胞内障碍至关重要。阳离子聚合物通过与带负电荷的核酸的静电相互作用形成多聚体，是一类很有前景的载体。通过固相辅助合成序列定义的阳离子低聚物，可以克服聚阳离子在毒性、异质性和多分散性方面的问题。这些中等大小的高度通用的核酸载体具有低细胞毒性，可以通过多种方式进行修饰和定制，以满足核酸结合、多聚体大小、屏蔽、靶向和货物细胞内释放的特定要求。通过这种方式，序列定义的阳离子低聚物可以模拟病毒的动态和生物响应行为。
