Systemic nanoparticle delivery of CRISPR-Cas9 ribonucleoproteins for effective tissue specific genome editing

CRISPR-Cas9 has emerged as a powerful technology that relies on Cas9/sgRNA ribonucleoprotein complexes (RNPs) to target and edit DNA. However, many therapeutic targets cannot currently be accessed due to the lack of carriers that can deliver RNPs systemically. Here, we report a generalizable methodology that allows engineering of modified lipid nanoparticles to efficiently deliver RNPs into cells and edit tissues including muscle, brain, liver, and lungs. Intravenous injection facilitated tissue-specific, multiplexed editing of six genes in mouse lungs. High carrier potency was leveraged to create organ-specific cancer models in livers and lungs of mice though facile knockout of multiple genes. The developed…

• CF
  Cystic Fibrosis Foundation

  Award: SIEGWA18XX0
• WF
  Welch Foundation

  Awards: 5P30CA142543, 1-0025, grant 1-0025, I-1855
• MF
  Moody Foundation
• CP
  Cancer Prevention and Research Institute of Texas
• UO
  University of Texas Southwestern Medical Center

  Award: 5P30CA142543
• VP
  Vertex Pharmaceuticals
• NI
  National Institutes of Health

  Awards: HL130253, 5P30CA142543, U54 HD 087351, HD 087351, AR-067294, R01 EB025192-01A1, EB025192
• NC
  National Cancer Institute

  Award: 5P30CA142543
• NI
  National Institute of Biomedical Imaging and Bioengineering

  Awards: EB025192-01A1, R01 EB025192-01A1