Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR–Cas9 ribonucleoprotein
Innovative Genomics Institute · University of California, Berkeley · +4 more institutions
Abstract
Lipid nanoparticle (LNP) delivery of clustered regularly interspaced short palindromic repeat (CRISPR) ribonucleoproteins (RNPs) could enable high-efficiency, low-toxicity and scalable in vivo genome editing if efficacious RNP-LNP complexes can be reliably produced. Here we engineer a thermostable Cas9 from Geobacillus stearothermophilus (GeoCas9) to generate iGeoCas9 variants capable of >100× more genome editing of cells and organs compared with the native GeoCas9 enzyme. Furthermore, iGeoCas9 RNP-LNP complexes edit a variety of cell types and induce homology-directed repair in cells receiving codelivered single-stranded DNA templates. Using tissue-selective LNP formulations, we observe genome-editing levels…
Citation impact
- FWCI
- 23.85
- Percentile
- 100%
- References
- 62
Authors
10- KCKai ChenCorresponding
Innovative Genomics Institute, University of California, Berkeley
- HHHesong Han
Innovative Genomics Institute, University of California, Berkeley
- SZSheng Zhao
Innovative Genomics Institute, University of California, Berkeley
- BXBryant Xu
Innovative Genomics Institute, University of California, Berkeley
- BYBoyan Yin
Innovative Genomics Institute, University of California, Berkeley
Topics & keywords
- Genome editing
- Cas9
- Ribonucleoprotein
- CRISPR
- Guide RNA
- Genome
- Biology
- Computational biology
Funding
- NSNational Science FoundationAwards: DE-AC02-05CH11231, 2334028
- HHHoward Hughes Medical InstituteAward: DE-AC02-05CH11231
- UDU.S. Department of EnergyAwards: -AC02-05CH11231, 05CH11231, B656358, 2553571, AC02-05CH11231, DE-AC02, DE-AC02-05CH11231, DE-AC02-
- CFCystic Fibrosis Foundation
- CICalifornia Institute for Regenerative MedicineAwards: DISC2-14045, DISC2-14097
- LSLife Sciences Research Foundation
- IGInnovative Genomics Institute
- ECEmerson Collective
- AVAdditional Ventures
- NINational Institutes of HealthAwards: UM1AI164559, U54AI170792, U01AI142817, U19AI171110, RM1HG009490, R01MH125979-01, DE-AC02-05CH11231, U19AI135990, UH3AI150552
- NHNational Heart, Lung, and Blood InstituteAward: R21HL173710
- NINational Institute of Mental HealthAwards: R01MH125979, R01MH125979-01
- NINational Institute of Allergy and Infectious DiseasesAwards: U19AI171110, U54AI170792, U19AI135990, U19NS132303, UM1AI164559, UH3AI150552
- NINational Institute of Diabetes and Digestive and Kidney Diseases
- NINational Institute of Neurological Disorders and StrokeAward: U19NS132303
- LLLawrence Livermore National LaboratoryAwards: DE-AC02-05CH11231, 24180