降低用于碱基编辑的脂质纳米颗粒中可电离脂质的比例。
Minimizing the ratio of ionizable lipid in lipid nanoparticles for base editing.
作者信息
Chen Qiubing, Wang Xuebin, Zhang Yizhou, Tian Ming, Duan Junyi, Zhang Ying, Yin Hao
机构信息
Departments of Urology and Laboratory Medicine, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
State Key Laboratory of Virology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School, Wuhan University, Wuhan 430071, China.
出版信息
Natl Sci Rev. 2024 Apr 3;11(6):nwae135. doi: 10.1093/nsr/nwae135. eCollection 2024 Jun.
Lipid nanoparticles (LNPs) have gained clinical approval as carriers for both siRNA and mRNA. Among the crucial components of LNPs, ionizable lipids play a pivotal role in determining the efficiency of RNA delivery. In this study, we synthesized a series of ionizable lipids, denoted as HTO, with a higher count of hydroxyl groups compared to SM-102. Remarkably, LNPs based on HTO12 lipid demonstrated comparable mRNA delivery efficiency and biosafety to those based on SM-102. However, the former reduced the ratio of ionizable lipid/total lipids to mRNA in LNPs by 2.5 times compared to SM-102. The HTO12 LNP efficiently encapsulated adenine base editor mRNA and sgRNA targeting , leading to substantial gene editing within the liver of mice and effective reduction of the target protein. Our study underscores that ionizable lipids with multiple hydroxyl groups may facilitate an improved lipid-to-mRNA ratio to minimize the dosage of ionizable lipids for delivery.
脂质纳米颗粒（LNPs）已作为小干扰RNA（siRNA）和信使核糖核酸（mRNA）的载体获得临床批准。在LNPs的关键组分中，可电离脂质在决定RNA递送效率方面起着关键作用。在本研究中，我们合成了一系列可电离脂质，命名为HTO，其羟基数量比SM-102更多。值得注意的是，基于HTO12脂质的LNPs在mRNA递送效率和生物安全性方面与基于SM-102的LNPs相当。然而，与SM-102相比，前者使LNPs中可电离脂质/总脂质与mRNA的比例降低了2.5倍。HTO12 LNP有效地包裹了腺嘌呤碱基编辑器mRNA和靶向的单向导RNA（sgRNA），导致小鼠肝脏内大量基因编辑并有效降低了靶蛋白。我们的研究强调，具有多个羟基的可电离脂质可能有助于提高脂质与mRNA的比例，以最小化可电离脂质用于递送的剂量。
Zotero 插件