核糖核酸
计算生物学
化学
分子动力学
纳米技术
细胞内
体外
体内
生物物理学
生物
生物化学
材料科学
遗传学
基因
计算化学
作者
Adiran Garaizar,Christian Díaz-Oviedo,Nina Zablowsky,Sami Rissanen,Johannes Köbberling,Jiawei Sun,Christoph Steiger,Patrick Steigemann,Florian A. Mann,Katharina Meier
标识
DOI:10.1073/pnas.2404555121
摘要
The use of lipid nanoparticles (LNPs) for therapeutic RNA delivery has gained significant interest, particularly highlighted by recent milestones such as the approval of Onpattro and two mRNA-based SARS-CoV-2 vaccines. However, despite substantial advancements in this field, our understanding of the structure and internal organization of RNA-LNPs –and their relationship to efficacy, both in vitro and in vivo– remains limited. In this study, we present a coarse-grained molecular dynamics (MD) approach that allows for the simulations of full-size LNPs. By analyzing MD-derived structural characteristics in conjunction with cellular experiments, we investigate the effect of critical parameters, such as pH and composition, on LNP structure and potency. Additionally, we examine the mobility and chemical environment within LNPs at a molecular level. Our findings highlight the significant impact that LNP composition and internal molecular mobility can have on key stages of LNP-based intracellular RNA delivery.
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