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
  • 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.
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-148049
    TT3
    98.0%, Lipid-like Compound
    target: Liposome
    Research Areas: Others