An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo.
An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo.
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DOI：
10.1021/acs.nanolett.5b03528
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发表时间：
2015-12-09
期刊：
影响因子：
10.8
通讯作者：
Dong Y
中科院分区：
文献类型：
--
作者：
Li B;Luo X;Deng B;Wang J;McComb DW;Shi Y;Gaensler KM;Tan X;Dunn AL;Kerlin BA;Dong Y
在临床前和临床研究中，基于mrna的疗法的全身递送仍然是一个具有挑战性的问题。在这里，我们描述了通过正交阵列设计开发的新型脂质样纳米颗粒（TT-LLNs），该纳米颗粒证明了编码荧光素酶的mRNA在体外的传递效率提高了350倍以上，同时显著减少了实验工作量。一种优化的TT3 LLN，称为O-TT3 LLN，能够将fix敲除小鼠的人因子IX （hFIX）水平恢复到正常的生理值。因此，这些基于mRNA的纳米材料值得进一步开发用于治疗应用。
Systemic delivery of mRNA-based therapeutics remains a challenging issue for preclinical and clinical studies. Here, we describe new lipid-like nanoparticles (TT-LLNs) developed through an orthogonal array design, which demonstrates improved delivery efficiency of mRNA encoding luciferase in vitro by over 350-fold with significantly reduced experimental workload. One optimized TT3 LLN, termed O-TT3 LLNs, was able to restore the human factor IX (hFIX) level to normal physiological values in FIX-knockout mice. Consequently, these mRNA based nanomaterials merit further development for therapeutic applications.