An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo
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- 作者：Bin Li ; Xiao Luo ; Binbin Deng ; Junfeng Wang ; David W. McComb ; Yimin Shi ; Karin M. L. Gaensler ; Xu Tan ; Amy L. Dunn ; Bryce A. Kerlin ; Yizhou Dong
- 刊名：Nano Letters
- 出版年：2015
- 出版时间：December 9, 2015
- 年：2015
- 卷：15
- 期：12
- 页码：8099-8107
- 全文大小：556K
- ISSN：1530-6992
文摘
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.