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Reversal of tumor malignization and modulation of cell behaviors through genome editing mediated by a multi-functional nanovector

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Abstract

To effectively reverse tumor malignization by genome editing, a multi-functional self-assembled nanovector for the delivery of a genome editing plasmid specifically to tumor cells was developed. The nanovector core consisting of protamine and calcium carbonate entrapping the CRISPR-Cas9 plasmid is decorated by aptamer incorporated heparin. Owing to a high affinity between a MUC1 specific aptamer and mucin 1 (MUC1) overexpressed in tumor cells as well as the interaction between AS1411 and nucleolin on the tumor cell surface and cell nuclei, the nanovector can target the nuclei of tumorous cells for the knockout of focal adhesion kinase (FAK). Notably, the genome editing mediated by our delivery systems can effectively modulate cell behaviors and thus reverse tumor malignization. Up-regulated p53, p16, p21, E-cadherin, CD80, MICA, MICB and Fas, together with down-regulated MMP-9, vimentin, VEGF, TGF-β, CD47 and CD133 in genome edited cells indicate that the genome editing system can inhibit cancerous cell growth, prevent tumor invasion and metastasis, reverse tumor-induced immune suppression, and inhibit cancer stemness. More importantly, the edited cells can maintain the modulated cellular function after succeeding subcultures.

Graphical abstract: Reversal of tumor malignization and modulation of cell behaviors through genome editing mediated by a multi-functional nanovector

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Publication details

The article was received on 09 Sep 2018, accepted on 30 Oct 2018 and first published on 31 Oct 2018


Article type: Paper
DOI: 10.1039/C8NR07321J
Citation: Nanoscale, 2018, Advance Article
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    Reversal of tumor malignization and modulation of cell behaviors through genome editing mediated by a multi-functional nanovector

    B. Liu, X. He, R. Zhuo and S. Cheng, Nanoscale, 2018, Advance Article , DOI: 10.1039/C8NR07321J

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