Advances in Optical Regulation of the CRISPR/Cas9 System

doi:10.6023/A24060192

Acta Chimica Sinica ›› 2024, Vol. 82 ›› Issue (11): 1180-1192.DOI: 10.6023/A24060192 Previous Articles

Review

CRISPR/Cas9系统的光学调控研究进展

薛煜雯^a, 李磊^b, 李美星^b^,^*(), 沈清明^b^,^*()

a 南京邮电大学省部共建有机电子与信息显示国家重点实验室化学与生命科学学院南京 210023
b 南京邮电大学省部共建有机电子与信息显示国家重点实验室材料科学与工程学院南京 210023

投稿日期:2024-06-12 发布日期:2024-10-08
通讯作者: 李美星, 沈清明

作者简介:

薛煜雯, 南京邮电大学化学与生命科学学院在读硕士研究生, 主要从事CRISPR/Cas13a近红外肿瘤诊疗纳米平台的构建及其应用研究.

李磊, 南京邮电大学材料与科学工程学院在读硕士研究生, 主要从事光控激活型分子荧光探针的设计及肿瘤靶向诊疗应用研究.

李美星, 博士, 副教授, 硕士生导师, 2018年博士毕业于南京大学, 同年入职南京邮电大学材料科学与工程学院, 主要从事化学生物传感及光学成像、单颗粒/单细胞分析等领域的基础和应用研究.

沈清明, 博士, 教授, 博士生导师, 江苏省“333高层次人才培养工程”中青年学术技术带头人, 江苏省青蓝工程优秀教学团队负责人. 2008年获南京大学理学博士学位, 2010年至今在南京邮电大学材料科学与工程学院工作. 主要从事功能纳米材料的设计合成、生物纳米探针的组装及医学成像、光学诊疗平台构筑及面向肿瘤诊疗的应用研究.

基金资助:
江苏省自然科学基金面上项目(BK20221326); 江苏省高等学校自然科学研究重大项目(20KJA430012); 江苏高校“青蓝工程”资助

Advances in Optical Regulation of the CRISPR/Cas9 System

Yuwen Xue^a, Lei Li^b, Meixing Li^b(), Qingming Shen^b()

a State Key Laboratory of Organic Electronics and Information Displays, School of Chemistry and Life Sciences, Nanjing University of Posts & Telecommunications, Nanjing 210023
b State Key Laboratory of Organic Electronics and Information Displays, College of Materials Science & Engineering, Nanjing University of Posts & Telecommunications, Nanjing 210023

Received:2024-06-12 Published:2024-10-08
Contact: ^*E-mail: iammxli@njupt.edu.cn; iamqmshen@njupt.edu.cn
Supported by:
Natural Science Foundation of Jiangsu Province(BK20221326); Natural Science Foundation of Jiangsu Higher Education Institutions(20KJA430012); Qing Lan Project of Jiangsu Province

CRISPR/Cas9 gene editing system consists of clustered regularly interspaced short palindromic repeats (CRISPR) sequences and CRISPR-associated protein 9 (Cas9), characterized by its simple structure, easy modification, and strong gene editing ability. It has great potential for application in genome editing, transcriptional perturbation, epigenetic regulation, and other fields. Despite its significant advantages in gene editing, the CRISPR/Cas9 system fails to achieve precise spatial and temporal control over the editing process and its cell and tissue-specific recognition capability requires improvement. The potential off-target phenomenon of genotoxicity will be further aggravated with increased Cas9 activity, greatly limiting its application in complex biological systems. Therefore, developing gene editing systems capable of precisely controlling the expression of multiple endogenous genes has become a hot topic of current CRISPR/Cas9 research. Light, as a non-invasive medium with high spatiotemporal resolution, is easy to regulate in terms of duration, location, wavelength, and intensity. Optical regulation, as a novel spatiotemporal regulation strategy of CRISPR/Cas9, has attracted much attention due to its characteristics of minimal toxic side effects, high spatiotemporal resolution, and real-time controllability. Optical regulation strategies can also be used in conjunction with imaging technologies such as fluorescence imaging and photoacoustic imaging to track the delivery process, greatly reducing the difficulty and safety risks of gene editing in vivo, thereby achieving visual delivery and precise spatiotemporal control of CRISPR systems. This review aims to summarize various optical modulation strategies employed in CRISPR/Cas9 system in recent years, evaluating the advantages and disadvantages of these strategies, and provide an outlook on the challenges and prospects of optical modulation in the CRISPR/Cas9 system.

Key words: CRISPR/Cas9, optical regulation, gene editing, cancer treatment, specificity

Cite this article

Yuwen Xue, Lei Li, Meixing Li, Qingming Shen. Advances in Optical Regulation of the CRISPR/Cas9 System[J]. Acta Chimica Sinica, 2024, 82(11): 1180-1192.

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Fig. & Tab. 20

Figure 1. Light activation diagram of cage Cas9[20]. Copyright ? 2015, American Chemical Society

Figure 2. Methods for light-modulating protein functions with small molecules and their applications on CRISPR/Cas9 modulation[29]. Copyright ?2023 SIOC, CAS, Shanghai, & WILEY-VCH GmbH

Figure 3. Schematic representation of the light-regulation of CRISPR/ Cas9-mediated DNA editing[31]. Copyright ? 2020 Wiley‐VCH GmbH

Figure 4. CRISPR-plus achieves photoactivatable blockade of Cas9-mediated DNA targeting[22]. Copyright ? 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim

Figure 5. Schematic of Cas9 deactivation mechanism[33]

Figure 6. Schematic depiction of the conformationally restricted crRNA principle[34]

Figure 7. Schematic illustration of the design of the G-quadruplex-based CRISPR photoswitch system[35]

Figure 8. Schematic of pSPN-mediated delivery and photoregulation of CRISPR/Cas9 gene editing under the NIR light irradiation[42]. Copyright ? 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim

Figure 10. Schematic illustration of the NIR light-controlled biomimetic nanoplatform for the delivery of Cas9 RNP for HBV gene editing[49]. Copyright ? 2022, The Author(s)

Figure 11. Schematic of the photoactivatable Cas9 (paCas9)[51]. Copyright ? 2015, Springer Nature America, Inc.

Figure 12. Schematic of engineering photoswitchable SpCas9[53]

Figure 13. Schematic of CASANOVA function[61]

Figure 14. Design of the optogenetic DNA methylation editing platform based on the CRISPR/Cas9 system[62]. Copyright ? 2021, American Chemical Society

Figure 15. Schematic of light-inducible transcriptional reprogramming device (CaRROT)[21]. Copyright ? 2018, American Chemical Society

Figure 16. Schematic of the FAST system[63]

Figure 17. Design of SPPF-Dex NPs for CRISPR/Cas9 delivery[23]. Copyright ? 2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim

Figure 18. Schematic illustration on the design of NIR-II laser-mediated delivery of CRISPR/Cas9 system[69]. Copyright ? 2021 Wiley‐VCH GmbH

Figure 20. Schematic illustration of the photothermal genome-editing strategy for cancer immunotherapy[74]. Copyright ? 2021 Wiley‐VCH GmbH

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CRISPR/Cas9系统的光学调控研究进展

Advances in Optical Regulation of the CRISPR/Cas9 System

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