RNA replicon delivery via lipid-complexed PRINT protein particles

Mol Pharm. 2013 Sep 3;10(9):3366-74. doi: 10.1021/mp400190z. Epub 2013 Aug 21.

Abstract

Herein we report the development of a nonviral lipid-complexed PRINT (particle replication in nonwetting templates) protein particle system (LPP particle) for RNA replicon delivery with a view toward RNA replicon-based vaccination. Cylindrical bovine serum albumin (BSA) particles (diameter (d) 1 μm, height (h) 1 μm) loaded with RNA replicon and stabilized with a fully reversible disulfide cross-linker were fabricated using PRINT technology. Highly efficient delivery of the particles to Vero cells was achieved by complexing particles with a mixture of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) lipids. Our data suggest that (1) this lipid-complexed protein particle is a promising system for delivery of RNA replicon-based vaccines and (2) it is necessary to use a degradable cross-linker for successful delivery of RNA replicon via protein-based particles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Fatty Acids, Monounsaturated / chemistry
  • Gene Transfer Techniques
  • Humans
  • Lipids / chemistry*
  • Phosphatidylethanolamines / chemistry
  • Quaternary Ammonium Compounds / chemistry
  • RNA / administration & dosage
  • RNA / chemistry
  • RNA / genetics*
  • Serum Albumin, Bovine / chemistry

Substances

  • 1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine
  • Fatty Acids, Monounsaturated
  • Lipids
  • Phosphatidylethanolamines
  • Quaternary Ammonium Compounds
  • Serum Albumin, Bovine
  • RNA
  • 1,2-dioleoyloxy-3-(trimethylammonium)propane