Effects of Local Structural Transformation of Lipid-Like Compounds on Delivery of Messenger RNA


Authors: B. Li, X. Luo, B. Deng, J.B. Giancola, D.W. McComb, T.D. Schmittgen and Y. Dong

Journal: Scientific Reports

DOI: 10.1038/srep22137

Publication - Abstract

February 26, 2016

mRNA Nucleic Acid Lipid Nanoparticles Genetic Medicine

Abstract:

Lipid-like nanoparticles (LLNs) have shown great potential for RNA delivery. Lipid-like compounds are key components in LLNs. In this study, we investigated the effects of local structural transformation of lipid-like compounds on delivery of messenger RNA. Our results showed that position change of functional groups on lipid-like compounds can dramatically improve delivery efficiency. We then optimized formulation ratios of TNT-b10 LLNs, a lead material, increasing delivery efficiency over 2-fold. More importantly, pegylated TNT-b10 LLNs is stable for over four weeks and is over 10-fold more efficient than that of its counterpart TNT-a10 LLNs. Additionally, the optimal formulation O-TNT-b10 LLNs is capable of delivering mRNA encoding luciferase in vivo. These results provide useful insights into the design of next generation LLNs for mRNA delivery.


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