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Minimizing the ratio of ionizable lipid in lipid nanoparticles for in vivo base editing

NSR. 2024-04; 
Qiubing Chen, Xuebin Wang, Yizhou Zhang, Ming Tian, Junyi Duan, Ying Zhang, Hao Yin
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Gene Synthesis ABE mRNA was produced by IVT with N1-methyl-pseudouridine modification. sgRNA with phosphorothioate and 2′-O-methyl modification at the 3' and 5' ends was from GenScript (Nanjing, China). Get A Quote

摘要

Lipid nanoparticles 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 to mRNA in LNPs by 2.5 times compared to SM-102. The HTO12 LNP efficiently encapsulated adenine base editor mRNA and sgRNA targeting Pcsk9, leading to substantial gene editing within the liver... More

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