Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA

被引：33
|
作者：
Li, Bin [1 ]
Luo, Xiao [1 ]
Deng, Binbin [2 ]
Giancola, JoLynn B. [3 ]
McComb, David W. [2 ]
Schmittgen, Thomas D. [4 ]
Dong, Yizhou [1 ]
机构：
[1] Ohio State Univ, Coll Pharm, Div Pharmaceut & Pharmaceut Chem, 500 W 12Th Ave, Columbus, OH 43210 USA
[2] Ohio State Univ, Ctr Electron Microscopy & Anal, Dept Mat Sci & Engn, Columbus, OH 43212 USA
[3] Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA
[4] Univ Florida, Coll Pharm, Div Pharmaceut, Gainesville, FL 32610 USA
来源：
SCIENTIFIC REPORTS | 2016年 / 6卷
关键词：
IN-VIVO; COMBINATORIAL LIBRARY; NANOPARTICLES; NANOMATERIALS; OPTIMIZATION; FORMULATIONS; EXPRESSION; CELLS;
D O I：
10.1038/srep22137
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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-b(10) LLNs, a lead material, increasing delivery efficiency over 2-fold. More importantly, pegylated TNT-b(10) LLNs is stable for over four weeks and is over 10-fold more efficient than that of its counterpart TNT-a(10) LLNs. Additionally, the optimal formulation O-TNT-b(10) 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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页数：8
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