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

被引：205

作者：

Li, Bin ^{[1
]}

Luo, Xiao ^{[1
]}

Deng, Binbin ^{[2
]}

Wang, Junfeng ^{[1
]}

McComb, David W. ^{[2
]}

Shi, Yimin ^{[3
]}

Gaensler, Karin M. L. ^{[3
]}

Tan, Xu ^{[4
]}

Dunn, Amy L. ^{[5
,6
]}

Kerlin, Bryce A. ^{[5
,6
,7
]}

Dong, Yizhou ^{[1
]}

机构：

[1] Ohio State Univ, Coll Pharm, Div Pharmaceut & Pharmaceut Chem, Columbus, OH 43210 USA

[2] Ohio State Univ, Dept Mat Sci & Engn, Ctr Electron Microscopy & Anal, Columbus, OH 43212 USA

[3] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[4] Tsinghua Univ, Sch Med, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China

[5] Nationwide Childrens Hosp, Div Hematol Oncol BMT, Columbus, OH 43205 USA

[6] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43205 USA

[7] Nationwide Childrens Hosp, Res Inst, Ctr Clin & Translat Res, Columbus, OH 43205 USA

来源：

NANO LETTERS | 2015年 / 15卷 / 12期

关键词：

Lipid-like nanoparticles; mRNA delivery; orthogonal array design; hemophilia; genetic disorders; SIRNA DELIVERY; VACCINATION TRIAL; DIRECT-INJECTION; GENE DELIVERY; DESIGN; HEMOPHILIA; THERAPEUTICS; EXPRESSION; VACCINES; THERAPY;

D O I：

10.1021/acs.nanolett.5b03528

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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

引用

页码：8099 / 8107

页数：9

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