Department of Materials Engineering, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Endocrinology. 2010 Feb;151(2):466-73. doi: 10.1210/en.2009-1045. Epub 2009 Dec 23.
Nucleic acid-based therapies offer great potential for treatment of a variety of diseases including cancer by modulating protein expression with DNA or small interfering RNA. However, realization of their full therapeutic potential is currently limited due to an inability to reach the target site in an active form. Identification of delivery barriers such as stability in circulation, resistance to degradation and entrapment in subcellular vesicles has led to development of sophisticated multifunctional synthetic polymers for forming ionic complexes with nucleic acids and also providing performance-enhancing features. The most promising designs comprise features to help increase stability in circulation and also contain functionality to aid in endosome escape of nucleic acid cargo after cellular internalization.
核酸治疗为治疗多种疾病提供了巨大的潜力，包括通过调节 DNA 或小干扰 RNA 表达来治疗癌症。然而，由于无法以活性形式到达靶位，它们的全部治疗潜力目前受到限制。识别递药障碍，如在循环中的稳定性、抵抗降解和被困在亚细胞囊泡中，导致了复杂的多功能合成聚合物的发展，这些聚合物可以与核酸形成离子复合物，并提供增强性能的特性。最有前途的设计包括帮助增加循环稳定性的特性，并且还包含有助于核酸货物在细胞内化后逃离内涵体的功能。
