Gene therapy is an important therapeutic strategy in the treatment of a wide range of genetic disorders. Polymers forming stable complexes with nucleic acids (NAs) are non-viral gene carriers. The self-assembly of polymers and nucleic acids is typically a complex process that involves many types of interaction at different scales. Electrostatic interaction, hydrophobic interaction, and hydrogen bonds are three important and prevalent interactions in the polymer/nucleic acid system. Electrostatic interactions and hydrogen bonds are the main driving forces for the condensation of nucleic acids, while hydrophobic interactions play a significant role in the cellular uptake and endosomal escape of polymer-nucleic acid complexes. To design high-efficiency polymer candidates for the DNA and siRNA delivery, it is necessary to have a detailed understanding of the interactions between them in solution. In this chapter, we survey the roles of the three important interactions between polymers and nucleic acids during the formation of polyplexes and summarize recent understandings of the linear polyelectrolyte–NA interactions and dendrimer–NA interactions. We also review recent progress optimizing the gene delivery system by tuning these interactions.

基因治疗是治疗多种遗传疾病的重要治疗策略。与核酸（NAs）形成稳定复合物的聚合物是非病毒基因载体。聚合物和核酸的自组装通常是一个复杂的过程，涉及不同规模的许多类型的相互作用。静电相互作用，疏水相互作用和氢键是聚合物/核酸体系中的三个重要且普遍的相互作用。静电相互作用和氢键是核酸缩合的主要驱动力，而疏水相互作用在聚合物-核酸复合物的细胞摄取和内体逃逸中起着重要作用。要设计用于DNA和siRNA输送的高效聚合物候选物，有必要对它们在解决方案中的相互作用有详细的了解。在本章中，我们调查了聚合物和核酸之间在复合物形成过程中三个重要相互作用的作用，并总结了对线性聚电解质-NA相互作用和树枝状聚合物-NA相互作用的最新理解。我们还回顾了通过调节这些相互作用优化基因传递系统的最新进展。