Citation: Yuqing Liu, Shiling Zhang, Kai Jiang, Shiyue Ding, Limei Xu, Yingqi Liu, Ting Wang, Fenfen Zheng, Weiwei Xiong, Jun-Jie Zhu. Near-infrared light responsive upconversion-DNA nanocapsules for remote-controlled CRISPR-Cas9 genome editing[J]. Chinese Chemical Letters, ;2025, 36(5): 110282. doi: 10.1016/j.cclet.2024.110282 shu

Near-infrared light responsive upconversion-DNA nanocapsules for remote-controlled CRISPR-Cas9 genome editing

Yuqing Liu ^a ,
Shiling Zhang ^a ,
Kai Jiang ^a ,
Shiyue Ding ^a ,
Limei Xu ^a ,
Yingqi Liu ^a ,
Ting Wang ^a ,
Fenfen Zheng ^{a, *,} ,
Weiwei Xiong ^{a, *,} ,
Jun-Jie Zhu ^{b, *,}

a.
School of Environmental & Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003, China
b.
State Key Laboratory of Analytical for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China

zhengfenfen@just.edu.cn

xiongweiwei@just.edu.cn

jjzhu@nju.edu.cn

Received Date: 4 February 2024
Revised Date: 19 June 2024
Accepted Date: 17 July 2024
Available Online: 18 July 2024

Figures(5)

As a renovator in the field of gene editing, CRISPR-Cas9 has demonstrated immense potential for advancing next-generation gene therapy owing to its simplicity and precision. However, this potential faces significant challenges primarily stemming from the difficulty in efficiently delivering large-sized genome editing system (including Cas9 protein and sgRNA) into targeted cells and spatiotemporally controlling their activity in vitro and in vivo. Therefore, the development of CRISPR/Cas9 nanovectors that integrate high loading capacity, efficient encapsulation and spatiotemporally-controlled release is highly desirable. Herein, we have engineered a near-infrared (NIR) light-activated upconversion-DNA nanocapsule for the remote control of CRISPR-Cas9 genome editing. The light-responsive upconversion-DNA nanocapsules consist of macroporous silica (mSiO₂) coated upconversion nanoparticles (UCNPs) and photocleavable o-nitrobenzyl-phosphate-modified DNA shells. The UCNPs act as a "nanotransducers" to convert NIR light (980 nm) into local ultraviolet light, thereby facilitating the cleavage of photosensitive DNA nanocapsules and enabling on-demand release of CRISPR-Cas9 encapsuled in the macroporous silica. Furthermore, by formulating a sgRNA targeted to a tumor gene (polo-like kinase-1, PLK-1), the CRISPR-Cas9 loaded UCNP-DNA nanocapsules (crUCNP-DNA nanocapsules) have effectively suppressed the proliferation of tumor cells through NIR light-activated gene editing both in vitro and in vivo. Overall, this UCNP-DNA nanocapsule holds tremendous potential for CRISPR-Cas9 delivery and remote-controlled gene editing in deep tissues, as well as the treatment of diverse diseases.
- UCNPs,
- CRISPR/Cas9,
- Gene editing,
- DNA nanocapsules,
- Near-infrared light
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