Protein and mRNA Delivery Enabled by Cholesteryl-Based Biodegradable Lipidoid Nanoparticles

Angew Chem Int Ed Engl. 2020 Aug 24;59(35):14957-14964. doi: 10.1002/anie.202004994. Epub 2020 Jun 15.


Developing safe and efficient delivery systems for therapeutic biomacromolecules is a long-standing challenge. Herein, we report a newly developed combinatorial library of cholesteryl-based disulfide bond-containing biodegradable cationic lipidoid nanoparticles. We have identified a subset of this library which is effective for protein and mRNA delivery in vitro and in vivo. These lipidoids showed comparable transfection efficacies but much lower cytotoxicities compared to the Lpf2k in vitro. In vivo studies in adult mice demonstrated the successful delivery of genome engineering protein and mRNA molecules in the skeletal muscle (via intramuscular injection), lung and spleen (via intravenous injection), and brain (via lateral ventricle infusion).

Keywords: genome engineering; lipidoid nanoparticle; mRNA delivery; protein delivery; stimuli responsive.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Humans
  • Mice
  • Nanoparticles / metabolism*
  • Proteins / chemical synthesis*
  • RNA, Messenger / chemistry*


  • Proteins
  • RNA, Messenger