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• W2783304391 abstract "The CRISPR/Cas9 gene editing technology holds promise for the treatment of multiple diseases. However, the inability to perform specific gene editing in targeted tissues and cells, which may cause off-target effects, is one of the critical bottlenecks for therapeutic application of CRISPR/Cas9. Herein, macrophage-specific promoter-driven Cas9 expression plasmids (pM458 and pM330) were constructed and encapsulated in cationic lipid-assisted PEG-b-PLGA nanoparticles (CLAN). The obtained nanoparticles encapsulating the CRISPR/Cas9 plasmids were able to specifically express Cas9 in macrophages as well as their precursor monocytes both in vitro and in vivo. More importantly, after further encoding a guide RNA targeting Ntn1 (sgNtn1) into the plasmid, the resultant CLANpM330/sgNtn1 successfully disrupted the Ntn1 gene in macrophages and their precursor monocytes in vivo, which reduced expression of netrin-1 (encoded by Ntn1) and subsequently improved type 2 diabetes (T2D) symptoms. Meanwhile, the Ntn1 gene was not disrupted in other cells due to specific expression of Cas9 by the CD68 promoter. This strategy provides alternative avenues for specific in vivo gene editing with the CRISPR/Cas9 system." @default.
• W2783304391 created "2018-01-26" @default.
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• W2783304391 date "2018-01-09" @default.
• W2783304391 modified "2023-10-17" @default.
• W2783304391 title "Macrophage-Specific <i>in Vivo</i> Gene Editing Using Cationic Lipid-Assisted Polymeric Nanoparticles" @default.
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• W2783304391 doi "https://doi.org/10.1021/acsnano.7b07874" @default.
• W2783304391 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29314827" @default.
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