2. Academic Validation
  3. Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA

Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA

  • Sci Rep. 2016 Feb 26:6:22137. doi: 10.1038/srep22137.
Bin Li 1,  Xiao Luo 1,  Binbin Deng 2,  JoLynn B Giancola 3,  David W McComb 2,  Thomas D Schmittgen 4,  Yizhou Dong 1
Affiliations

Affiliations

  • 1 Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
  • 2 Center for Electron Microscopy and Analysis, Department of Materials Science and Engineering, The Ohio State University, Columbus, Ohio 43212, USA.
  • 3 Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, USA.
  • 4 Division of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, USA.
PMID: 26916931 DOI: 10.1038/srep22137
Abstract

Lipid-like nanoparticles (LLNs) have shown great potential for RNA delivery. Lipid-like compounds are key components in LLNs. In this study, we investigated the effects of local structural transformation of lipid-like compounds on delivery of messenger RNA. Our results showed that position change of functional groups on lipid-like compounds can dramatically improve delivery efficiency. We then optimized formulation ratios of TNT-b10 LLNs, a lead material, increasing delivery efficiency over 2-fold. More importantly, pegylated TNT-b10 LLNs is stable for over four weeks and is over 10-fold more efficient than that of its counterpart TNT-a10 LLNs. Additionally, the optimal formulation O-TNT-b10 LLNs is capable of delivering mRNA encoding luciferase in vivo. These results provide useful insights into the design of next generation LLNs for mRNA delivery.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-159710
    Ionizable Lipid