Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles

A central challenge to the development of protein-based therapeutics is the inefficiency of delivery of protein cargo across the mammalian cell membrane, including escape from endosomes. Here we report that combining bioreducible lipid nanoparticles with negatively supercharged Cre recombinase or anionic Cas9:single-guide (sg)RNA complexes drives the electrostatic assembly of nanoparticles that mediate potent protein delivery and genome editing. These bioreducible lipids efficiently deliver protein cargo into cells, facilitate the escape of protein from endosomes in response to the reductive intracellular environment, and direct protein to its intracellular target sites. The delivery of supercharged Cre…

• NS
  National Science Foundation

  Award: DMR 1452122
• FF
  Foundation for the National Institutes of Health

  Award: R01 GM095501
• AD
  American Diabetes Association

  Award: 7-13-JF-61
• AC
  American Cancer Society

  Award: RSG-09-174-01-CCE