用于近红外光激活基因编辑和癌症基因治疗的半导体聚合物纳米CRISPR

A Semiconducting Polymer NanoCRISPR for Near-Infrared Photoactivatable Gene Editing and Cancer Gene Therapy.

作者信息

Liu Yue, Li Fei, Lyu Yan, Wang Fengshuo, Lee Leo Tsz On, He Shasha, Guo Zhong, Li Jingchao

机构信息

State Key Laboratory of Advanced Fiber Materials, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China.

State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

出版信息

Nano Lett. 2025 Mar 19;25(11):4518-4525. doi: 10.1021/acs.nanolett.5c00285. Epub 2025 Mar 7.

DOI:10.1021/acs.nanolett.5c00285

PMID:40053823

Abstract

Clustered regularly interspaced short palindromic repeat (CRISPR) gene editing has poor efficacy and off-target side effect concerns. We herein report a semiconducting polymer (SP)-based nanoCRISPR system to improve CRISPR delivery efficacy and allow for near-infrared (NIR) photoactivatable gene editing for cancer therapy. An amphiphilic SP acts as a photothermal converter, and its backbone is grafted with single-stranded deoxyribonucleic acid (DNA), which enables hybridization with single guide ribonucleic acid (sgRNA) via complementary base pairing to form sgRNA/SP-DNA. This sgRNA/SP-DNA nanosystem (nanoCRISPR) can effectively deliver sgRNA into cells and generate heat under NIR laser irradiation via the photothermal effect. The localized heat triggers the dissociation of single-stranded DNA and sgRNA to control the release of sgRNA, thereby achieving precise regulation of CRISPR activity. This NIR photoactivatable gene editing technology is able to precisely regulate the expression of green fluorescent protein (GFP) and polo-like kinase 1 (PLK1) gene for precision gene therapy.

摘要

成簇规律间隔短回文重复序列（CRISPR）基因编辑存在疗效不佳和脱靶副作用问题。我们在此报告一种基于半导体聚合物（SP）的纳米CRISPR系统，以提高CRISPR递送效率，并实现用于癌症治疗的近红外（NIR）光激活基因编辑。一种两亲性SP作为光热转换器，其主链接枝有单链脱氧核糖核酸（DNA），这使其能够通过互补碱基配对与单向导核糖核酸（sgRNA）杂交，形成sgRNA/SP-DNA。这种sgRNA/SP-DNA纳米系统（纳米CRISPR）能够有效地将sgRNA递送至细胞中，并在近红外激光照射下通过光热效应产生热量。局部热量触发单链DNA和sgRNA的解离，以控制sgRNA的释放，从而实现对CRISPR活性的精确调控。这种近红外光激活基因编辑技术能够精确调控绿色荧光蛋白（GFP）和波罗样激酶1（PLK1）基因的表达，用于精准基因治疗。