A Single Administration of CRISPR/Cas9 Lipid Nanoparticles Achieves Robust and Persistent In Vivo Genome Editing.
By Jonathan D. Finn, A. R. Smith, Mihir Patel, L. Shaw, Madeleine R. Youniss, J. V. van Heteren, Tanner Dirstine, Corey Ciullo, R. Lescarbeau, Jessica Seitzer and 13 more. Cell Reports, 2018
757 citations recorded by the source corpus.
The development of clinically viable delivery methods presents one of the greatest challenges in the therapeutic application of CRISPR/Cas9 mediated genome editing. Here, we report the development of a lipid nanoparticle (LNP)-mediated delivery system that, with a single administration, enabled significant editing of the mouse transthyretin (Ttr) gene in the liver, with a >97% reduction in serum protein levels that persisted for at least 12 months. These results were achieved with an LNP delivery system that was biodegradable and well tolerated. The LNP delivery system was combined with a sgRNA having a chemical modification pattern that was important for high levels of in vivo activity. The formulation was similarly effective in a rat model. Our work demonstrates that this LNP system can deliver CRISPR/Cas9 components to achieve clinically relevant levels of in vivo genome editing with a concomitant reduction of TTR serum protein, highlighting the potential of this system as an effective genome editing platform.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/583a89eacf6631c0427c7f699c2e593c154082bb
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In Molecular Biology
Citations in the corpus
- Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018, background): “In a recent report, a lipid nanoparticle (LNP-INT01) mediated effective delivery of both Cas9 mRNA and chemically modified sgRNA in vivo [116].”
- Engineered biomaterials for in situ tissue regeneration (2020, neutral): “These include lipid nanoparticles 100 , exosome-liposomes 101 , PEGylated helical polypeptide nanoparticles 102 , lipid-coated gold nanoparticles 103 and lipid-coated PEG-PLGA nanoparticles 103 .”