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
  • 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.

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