化学
连接器
体内
内化
脂肪酸
生物化学
体外
内吞作用
寡核苷酸
共轭体系
部分
细胞
立体化学
DNA
有机化学
生物
聚合物
生物技术
计算机科学
操作系统
作者
Yuya Tanaka,Yurika Tanioku,Taisuke Nakayama,Kotomi Aso,Takao Yamaguchi,Haruhiko Kamada,Satoshi Obika
标识
DOI:10.1016/j.bmc.2023.117192
摘要
Herein, we describe the design and synthesis of multi-conjugatable fatty acid monomer phosphoramidites and their conjugation to antisense oligonucleotides (ASOs). Multivalent long-chain fatty acid conjugation improved the cellular uptake of ASOs but decreased in vitro activity due to alterations in physical properties and cellular localization. In addition, multivalently fatty acid-conjugated ASOs showed different organ specificity compared with that of unconjugated ASO in in vivo experiment. Although optimization of the linker structure between the fatty acid moiety and the ASO may be required, divalent long-chain fatty acid conjugation provides a new approach to increase endocytosis, thereby potentially improving the activity of therapeutic ASOs.
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