Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA.
Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA.
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DOI：
10.1038/srep22137
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发表时间：
2016-02-26
影响因子：
4.6
通讯作者：
Dong Y
中科院分区：
文献类型：
--
作者：
Li B;Luo X;Deng B;Giancola JB;McComb DW;Schmittgen TD;Dong Y
类脂纳米粒子 (LLN) 在 RNA 递送方面显示出巨大的潜力。类脂化合物是 LLN 的关键成分。在这项研究中，我们研究了类脂化合物的局部结构转变对信使 RNA 传递的影响。我们的结果表明，类脂化合物上官能团的位置变化可以显着提高递送效率。然后，我们优化了 TNT-b10 LLN（一种先导材料）的配方比例，将输送效率提高了 2 倍以上。更重要的是，聚乙二醇化 TNT-b10 LLN 可稳定超过 4 周，并且效率比对应的 TNT-a10 LLN 高 10 倍以上。此外，最佳配方 O-TNT-b10 LLN 能够在体内递送编码荧光素酶的 mRNA。这些结果为下一代 mRNA 递送 LLN 的设计提供了有用的见解。
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.