Efficient ex vivo delivery of chemically modified messenger RNA using lipofection and magnetofection

Biochem Biophys Res Commun. 2017 Jan 22;482(4):796-801. doi: 10.1016/j.bbrc.2016.11.113. Epub 2016 Nov 22.

Abstract

Recently, chemically modified mRNA (cmRNA) therapeutics have been the subject of extensive application-oriented research in both academia and industry as a safer alternative for gene and recombinant protein therapies. However, the lack of an efficient delivery system hinders widespread application. Here we used ∼100-nm lipoplexes and magnetic lipoplexes that can protect cmRNA from RNases and efficiently deliver it into muscle and fat tissues as well as to the endothelium of the carotid artery. Establishing magnetofection for ex vivo cmRNA delivery for the first time, we suggest this method for potential enhanced and targeted delivery of cmRNA. This study introduces optimal cmRNA complexes with high ex vivo efficiency as good candidates for further in vivo cmRNA delivery.

Keywords: Chemically modified mRNA (cmRNA); Lipoplex; Magnetofection; cmRNA delivery system.

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Endothelial Cells / metabolism
  • Lipids / chemistry*
  • Liposomes / chemistry
  • Magnetics / methods*
  • Magnetite Nanoparticles / chemistry*
  • Mice
  • Muscles / metabolism
  • NIH 3T3 Cells
  • RNA, Messenger / administration & dosage*
  • RNA, Messenger / chemistry*
  • RNA, Messenger / genetics
  • Sheep
  • Swine
  • Transfection / methods*

Substances

  • Lipids
  • Liposomes
  • Magnetite Nanoparticles
  • RNA, Messenger