Hydrophobicity of Lipid-Conjugated siRNAs Predicts Productive Loading to Small Extracellular Vesicles

Mol Ther. 2018 Jun 6;26(6):1520-1528. doi: 10.1016/j.ymthe.2018.03.019. Epub 2018 Apr 4.

Abstract

Small extracellular vesicles (sEVs) show promise as natural nano-devices for delivery of therapeutic RNA, but efficient loading of therapeutic RNA remains a challenge. We have recently shown that the attachment of cholesterol to small interfering RNAs (siRNAs) enables efficient and productive loading into sEVs. Here, we systematically explore the ability of lipid conjugates-fatty acids, sterols, and vitamins-to load siRNAs into sEVs and support gene silencing in primary neurons. Hydrophobicity of the conjugated siRNAs defined loading efficiency and the silencing activity of siRNA-sEVs complexes. Vitamin-E-conjugated siRNA supported the best loading into sEVs and productive RNA delivery to neurons.

Keywords: hydrophobicity; lipid-conjugated siRNA; small extracellular vesicles.

Publication types

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

MeSH terms

  • Cells, Cultured
  • Extracellular Vesicles / chemistry*
  • Gene Silencing / physiology
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Lipids / chemistry*
  • RNA Interference
  • RNA, Small Interfering / chemistry*

Substances

  • Lipids
  • RNA, Small Interfering