Issue 5, 2024

A quaternary ammonium-based nanosystem enables delivery of CRISPR/Cas9 for cancer therapy

Abstract

Genome editing mediated by CRISPR/Cas9 is an attractive weapon for cancer therapy. However, in vivo delivery of CRISPR/Cas9 components to achieve therapeutic efficiency is still challenging. Herein, a quaternary ammonium-functionalized poly(L-lysine) and a cholesterol-modified PEG (QNP) were self-assembled with a negatively charged CRISPR Cas9/sgRNA ribonucleoprotein (RNP) to form a ternary complex (QNP/RNP). Such a delivery system of QNP exhibited multiplex genome editing capabilities in vitro (e.g., the GFP gene and the PLK1 gene). In addition, QNP/RNPPLK1 containing PLK1 sgRNA led to 30.99% of genome editing efficiency in MCF-7 cells with negligible cytotoxicity of the carrier. QNP/RNPPLK1, which was capable of simultaneously inhibiting cell proliferation, mediating cell cycle arrest and downregulating expression of PLK1, held great in vitro therapeutic efficiency. Moreover, QNP/RNPPLK1 exhibited outstanding accumulation in tumors and high biocompatibility in vivo. In an MCF-7 xenograft animal model, QNP/RNPPLK1 showed excellent anti-tumor efficacy and achieved 17.75% indels ratio. This work showcases the successful delivery of CRISPR Cas9/sgRNA RNP with enhanced genome editing efficiency and provides a potential on-demand strategy for cancer therapy.

Graphical abstract: A quaternary ammonium-based nanosystem enables delivery of CRISPR/Cas9 for cancer therapy

Supplementary files

Article information

Article type
Paper
Submitted
09 Okt. 2023
Accepted
04 Janv. 2024
First published
11 Janv. 2024
This article is Open Access
Creative Commons BY-NC license

Biomater. Sci., 2024,12, 1197-1210

A quaternary ammonium-based nanosystem enables delivery of CRISPR/Cas9 for cancer therapy

M. Zhang, S. Sun, X. Liang, Z. Liu, J. Yin, Q. Li and S. Yang, Biomater. Sci., 2024, 12, 1197 DOI: 10.1039/D3BM01629C

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