Department of Pharmaceutics, Center for Research Development and Evaluation of Pharmaceutical Excipients and Generic Drugs, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
Top Curr Chem (Cham). 2018 Jan 15;376(1):2. doi: 10.1007/s41061-017-0183-y.
Gene therapy requires successful delivery of therapeutic nucleic acids into target cells; thus, efficient and safe gene delivery carriers are crucial to its success. Although many polymeric materials have shown their potential as effective nucleic acid carriers, the inherent heterogeneity and polydispersity of these polymers hinder their application in clinical studies because of difficulties in their further precise modification, structure-activity relationship study, as well as consistent manufacturing. Therefore, precisely defined polymers, with potential for site-specific optimization according to structure-activity relationship information and highly controllable production, have been extensively investigated. In this review, we focus on the design and development of precisely defined polymers for efficient gene delivery, illustrated with examples including dendrimers, peptide-based polymers, and sequence-defined oligoaminoamide oligomers.
基因治疗需要将治疗性核酸有效地递送到靶细胞中;因此,高效且安全的基因传递载体对于基因治疗的成功至关重要。虽然许多聚合物材料已显示出作为有效核酸载体的潜力,但由于其进一步精确修饰、结构-活性关系研究以及一致制造方面的困难,这些聚合物的固有异质性和多分散性阻碍了它们在临床研究中的应用。因此,具有根据结构-活性关系信息进行定点优化以及高度可控生产潜力的精确定义的聚合物已得到广泛研究。在本综述中,我们重点介绍了用于高效基因传递的精确定义聚合物的设计和开发,并举例说明了树状大分子、基于肽的聚合物和序列定义的寡聚氨基酸酰胺低聚物。