Kim Hyun Jin, Kim Ahram, Miyata Kanjiro
Department of Biological Engineering, College of Engineering, Inha University, 100 Inha-ro, Michuhol-gu, Incheon, 22212, South Korea; Department of Biological Sciences and Bioengineering, Inha University, 100 Inha-ro, Michuhol-gu, Incheon, 22212, South Korea.
Research Center for Functional Materials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki, 305-0044, Japan.
Drug Metab Pharmacokinet. 2022 Feb;42:100428. doi: 10.1016/j.dmpk.2021.100428. Epub 2021 Oct 30.
Recent progress in the design of cationic lipids and polymers has successfully translated nucleic acid drugs into clinical applications, such as the treatment of liver diseases and the prevention of virus infection. Small or large libraries of delivery molecules have been used to find the key chemical structures to protect nucleic acids from nucleases in the extracellular milieu and to facilitate the endosomal escape after endocytosis. This review introduces three essential design parameters (i.e., acid dissociation constant, hydrophobicity, and biodegradability) to develop synthetic molecules for nucleic acid delivery. The significance and mechanism of each parameter are described based on the results obtained from in vitro and in vivo evaluations. Other design parameters were then discussed to create the next generation of delivery molecules for future nucleic acid therapeutics.
阳离子脂质体和聚合物设计方面的最新进展已成功地将核酸药物转化为临床应用，如用于治疗肝脏疾病和预防病毒感染。大量的递送分子文库已被用于寻找关键化学结构，以保护核酸在细胞外环境中免受核酸酶的破坏，并促进内吞作用后从内涵体逃逸。本综述介绍了开发用于核酸递送的合成分子的三个基本设计参数（即酸解离常数、疏水性和生物降解性）。基于体外和体内评估结果描述了每个参数的意义和机制。随后讨论了其他设计参数，以创造用于未来核酸治疗的下一代递送分子。
