核糖核酸
肝细胞
化学
体内
肝星状细胞
细胞生物学
细胞
聚乙二醇
体外
去唾液酸糖蛋白受体
基因传递
生物化学
生物
转染
基因
生物技术
内分泌学
作者
M. Kim,Michaela Jeong,Sun Hur,Y. Cho,J. Park,Hye Ri Jung,Yongho Seo,Hyeonju Woo,Keonwook Nam,K. Lee,H. Lee
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2021-02-26
卷期号:7 (9)
被引量:142
标识
DOI:10.1126/sciadv.abf4398
摘要
Ionizable lipid nanoparticles (LNPs) have been widely used for in vivo delivery of RNA therapeutics into the liver. However, a main challenge remains to develop LNP formulations for selective delivery of RNA into certain types of liver cells, such as hepatocytes and liver sinusoidal endothelial cells (LSECs). Here, we report the engineered LNPs for the targeted delivery of RNA into hepatocytes and LSECs. The effects of particle size and polyethylene glycol-lipid content in the LNPs were evaluated for the hepatocyte-specific delivery of mRNA by ApoE-mediated cellular uptake through low-density lipoprotein receptors. Targeted delivery of RNA to LSECs was further investigated using active ligands. Incorporation of mannose allowed the selective delivery of RNA to LSECs, while minimizing the unwanted cellular uptake by hepatocytes. These results demonstrate that engineered LNPs have great potential for the cell type-specific delivery of RNA into the liver and other tissues.
科研通智能强力驱动
Strongly Powered by AbleSci AI