2. Academic Validation
  3. 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

  • Nano Lett. 2015 Dec 9;15(12):8099-107. doi: 10.1021/acs.nanolett.5b03528.
Bin Li 1,  Xiao Luo 1,  Binbin Deng 2,  Junfeng Wang 1,  David W McComb 2,  Yimin Shi 3,  Karin M L Gaensler 3,  Xu Tan 4,  Amy L Dunn 5 6,  Bryce A Kerlin 5 6 7,  Yizhou Dong 1
Affiliations

Affiliations

  • 1 Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University , Columbus, Ohio 43210, United States.
  • 2 Center for Electron Microscopy and Analysis, Department of Materials Science and Engineering, The Ohio State University , Columbus, Ohio 43212, United States.
  • 3 Department of Medicine, University of California-San Francisco , San Francisco, California 94143, United States.
  • 4 Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University , Beijing 100084, China.
  • 5 Division of Hematology/Oncology/BMT, Nationwide Children's Hospital , Columbus, Ohio 43205, United States.
  • 6 Department of Pediatrics, College of Medicine, The Ohio State University , Columbus, Ohio 43205, United States.
  • 7 Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital , Columbus, Ohio 43205, United States.
PMID: 26529392 DOI: 10.1021/acs.nanolett.5b03528
Abstract

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.

Keywords

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

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