An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo

作者：Li, Bin; Luo, Xiao; Deng, Binbin; Wang, Junfeng; McComb, David W.; Shi, Yimin; Gaensler, Karin M. L.; Tan, Xu; Dunn, Amy L.; Kerlin, Bryce A.; Dong, Yizhou^*

来源：Nano Letters, 2015, 15(12): 8099-8107.

DOI：10.1021/acs.nanolett.5b03528

• Lipid-like nanoparticles
• mRNA delivery
• orthogonal array design
• hemophilia
• genetic disorders

Systemic delivery of mRNA-based therapeutics remains a challenging issue for preclinical and clinical studies. Here, we describe new lipid-like nanopartides (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 TT3 LLNs, was able to restore the human factor IX (hFIX) level to normal physiological values in FIX-knockout mice. Consequently, development for therapeutic applications. these mRNA based nanomaterials merit further

• 出版日期2015-12
• 单位清华大学