Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 113; no. 11; pp. 2868 - 2873
• Main Authors: Wang, Ming, Zuris, John A., Meng, Fantao, Rees, Holly, Sun, Shuo, Deng, Pu, Han, Yong, Gao, Xue, Pouli, Dimitra, Wu, Qi, Georgakoudi, Irene, Liu, David R., Xu, Qiaobing
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 15.03.2016; National Acad Sciences
• Subjects: Animals; Bacterial Proteins - administration & dosage; Bacterial Proteins - genetics; Ceramides - chemistry; Cholesterol - chemistry; CRISPR-Cas Systems; Drug Carriers; Endocytosis; Endonucleases - administration & dosage; Endonucleases - genetics; Endosomes - metabolism; Gene Knockout Techniques; Genes, Reporter; Genes, Synthetic; Genetic Engineering - methods; Genomes; Green Fluorescent Proteins - biosynthesis; Green Fluorescent Proteins - genetics; HeLa Cells; Humans; Hypothalamus - metabolism; Integrases - administration & dosage; Integrases - genetics; Lipids; Lipids - administration & dosage; Lipids - chemical synthesis; Lipids - chemistry; Luminescent Proteins - biosynthesis; Luminescent Proteins - genetics; Mice; Molecular Structure; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanoparticles - metabolism; Nanoparticles - toxicity; Phosphatidylethanolamines - chemistry; Physical Sciences; Proteins; Recombinant Proteins - biosynthesis; Recombination, Genetic; Ribonucleic acid; RNA; RNA - genetics; Static Electricity; Structure-Activity Relationship; Thalamus - metabolism; genome editing; lipid nanoparticle; CRISPR/Cas9; protein delivery; Cre recombinase

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 an...