Rational Engineering of a Designed Protein Cage for siRNA Delivery

J Am Chem Soc. 2018 Aug 22;140(33):10439-10442. doi: 10.1021/jacs.8b06442. Epub 2018 Aug 9.


Oligonucleotide therapeutics have transformative potential in modern medicine but are poor drug candidates in themselves unless fitted with compensatory carrier systems. We describe a simple approach to transform a designed porous protein cage into a nucleic acid delivery vehicle. By introducing arginine mutations to the lumenal surface, a positively supercharged capsule is created, which can encapsidate oligonucleotides in vitro with high binding affinity. We demonstrate that the siRNA-loaded cage is taken up by mammalian cells and releases its cargo to induce RNAi and knockdown gene expression. These general concepts could also be applied to alternative scaffold designs, expediting the development of artificial protein cages toward delivery applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Electrophoretic Mobility Shift Assay
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Protein Engineering*
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics


  • RNA, Small Interfering