CRISPR/Cas9系统的光学调控研究进展
 |
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. |
收稿日期: 2024-06-12
网络出版日期: 2024-10-09
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
Received date: 2024-06-12
Online published: 2024-10-09
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基因编辑系统由规律成簇的间隔短回文重复(Clustered regularly interspaced short palindromic repeats, CRISPR)序列和CRISPR-associated protein 9 (Cas9蛋白)组成, 具有结构简单、易于改造、基因编辑能力强等特点, 在基因组编辑、转录干扰、表观遗传调控等领域具有广泛的应用潜力. 尽管CRISPR/Cas9基因编辑系统在基因编辑方面具有明显优势, 但仍无法实现对基因编辑过程的精确时空控制. 另外, 对肿瘤细胞及特定病理组织的特异性还有待提升. 其潜在的脱靶现象所带来的基因毒性也会随着Cas9活性的增强而进一步加剧, 从而极大地限制了其在复杂生物系统中的应用. 因此, 制备能够精确控制多种内源性基因表达的基因编辑系统成为当前CRISPR/Cas9研究的热点. 光, 作为一种具备高时空分辨率且非侵入性的媒介, 其持续时间、位置、波长以及强度均易于调控. 光学调控作为一种CRISPR/Cas9新型时空调控策略, 因其具有毒副作用小、高时空分辨率以及实时可控等特点而备受人们关注. 光学调控策略还可以配合荧光成像、光声成像等影像技术追踪其递送过程, 能够极大降低体内基因编辑过程的控制难度和安全风险, 从而实现CRISPR系统的可视化递送与精准时空控制. 本文旨在综述近年来CRISPR/Cas9系统中采用的各种光学调控策略, 评估这些策略的优缺点, 并对CRISPR/Cas9系统中光学调控的挑战和发展前景进行展望.
关键词： CRISPR/Cas9; 光学调控; 基因编辑; 肿瘤治疗; 特异性
薛煜雯 , 李磊 , 李美星 , 沈清明 . CRISPR/Cas9系统的光学调控研究进展[J]. 化学学报, 2024 , 82(11) : 1180 -1192 . DOI: 10.6023/A24060192
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
| [1] | Jinek, M.; Chylinski, K.; Fonfara, I.; Hauer, M.; Doudna, J. A.; Charpentier, E. Science 2012, 337, 816. |
| [2] | Cong, L.; Ran, F. A.; Cox, D.; Lin, S.; Barretto, R.; Habib, N.; Hsu, P. D.; Wu, X.; Jiang, W.; Marraffini, L. A.; Zhang, F. Science 2013, 339, 819. |
| [3] | Knott, G. J.; Doudna, J. A. Science 2018, 361, 866. |
| [4] | Gallagher, D. N.; Haber, J. E. ACS Chem. Biol. 2018, 13, 397. |
| [5] | Richardson, C. D.; Ray, G. J.; DeWitt, M. A.; Curie, G. L.; Corn, J. E. Nat. Biotechnol. 2016, 34, 339. |
| [6] | Fu, F.; Xiong, W.; Xu, X.; Liu, Y.; Li, M.; Qi, Q.; Liu, X.; Zhang, Y.; Tian, T.; Zhou, X. Chin. J. Chem. 2024, 42, 2305. |
| [7] | Jiang, F.; Doudna, J. A. Annu. Rev. Biophys. 2017, 46, 505. |
| [8] | Urnov, F. D. CRISPR J. 2018, 1, 34. |
| [9] | Qiao, Y.; Zhang, Q.; Chen, D.; Liu, M.; Liu, W. Chin. J. Org. Chem. 2021, 41, 4279 (in Chinese). |
| [9] | (乔怡, 张庆林, 陈单丹, 刘美娜, 刘文, 有机化学, 2021, 41, 4279.) |
| [10] | Hu, J. H.; Davis, K. M.; Liu, D. R. Cell Chem. Biol. 2016, 23, 57. |
| [11] | Wan, T.; Pan, Q.; Liu, C.; Guo, J.; Li, B.; Yan, X.; Cheng, Y.; Ping, Y. Nano Lett. 2021, 21, 9761. |
| [12] | Li, B.; Niu, Y.; Ji, W.; Dong, Y. Trends Pharmacol. Sci. 2020, 41, 55. |
| [13] | Bhardwaj, S.; Kesari, K. K.; Rachamalla, M.; Mani, S.; Ashraf, G. M.; Jha, S. K.; Kumar, P.; Ambasta, R. K.; Dureja, H.; Devkota, H. P.; Gupta, G.; Chellappan, D. K.; Singh, S. K.; Dua, K.; Ruokolainen, J.; Kamal, M. A.; Ojha, S.; Jha, N. K. J. Adv. Res. 2021, 40, 207. |
| [14] | Vakulskas, C. A.; Behlke, M. A. Nucleic Acid Ther. 2019, 29, 167. |
| [15] | Maji, B.; Gangopadhyay, S. A.; Lee, M.; Shi, M.; Wu, P.; Heler, R.; Mok, B.; Lim, D.; Siriwardena, S. U.; Paul, B.; Dan?ík, V.; Vetere, A.; Mesleh, M. F.; Marraffini, L. A.; Liu, D. R.; Clemons, P. A.; Wagner, B. K.; Choudhary, A. Cell 2019, 177, 1067. |
| [16] | Zhuo, C.; Zhang, J.; Lee, J. H.; Jiao, J.; Cheng, D.; Liu, L.; Kim, H.-W.; Tao, Y.; Li, M. Signal Transduct. Target. Ther. 2021, 6, 238. |
| [17] | Xu, W.; Wang, D.; Tang, B. Z. Angew. Chem. Int. Ed. 2021, 60, 7476. |
| [18] | He, S.; Song, J.; Qu, J.; Cheng, Z. Chem. Soc. Rev. 2018, 47, 4258. |
| [19] | Dolmans, D. E.; Fukumura, D.; Jain, R. K. Nat. Rev. Cancer. 2003, 3, 380. |
| [20] | Hemphill, J.; Borchardt, E. K.; Brown, K.; Asokan, A.; Deiters, A. J. Am. Chem. Soc. 2015, 137, 5642. |
| [21] | Nguyen, N. T.; He, L.; Martinez-Moczygemba, M.; Huang, Y.; Zhou, Y. ACS Synth. Biol. 2018, 7, 814. |
| [22] | Jain, P. K.; Ramanan, V.; Schepers, A. G.; Dalvie, N. S.; Panda, A.; Fleming, H. E.; Bhatia, S. N. Angew. Chem. Int. Ed. 2016, 55, 12440. |
| [23] | Li, L.; Yang, Z.; Zhu, S.; He, L.; Fan, W.; Tang, W.; Zou, J.; Shen, Z.; Zhang, M.; Tang, L.; Dai, Y.; Niu, G.; Hu, S.; Chen, X. Adv. Mater. 2019, 31, e1901187. |
| [24] | Nishimasu, H.; Ran, F. A.; Hsu, P. D.; Konermann, S.; Shehata, S. I.; Dohmae, N.; Ishitani, R.; Zhang, F.; Nureki, O. Cell 2014, 156, 935. |
| [25] | Chen, Y.; Yan, X.; Ping, Y. ACS Mater. Lett. 2020, 2, 644. |
| [26] | Davis, K. M.; Pattanayak, V.; Thompson, D. B.; Zuris, J. A.; Liu, D. R. Nat. Chem. Biol. 2015, 11, 316. |
| [27] | Shin, J.; Jiang, F.; Liu, J.; Bray, N. L.; Rauch, B. J.; Baik, S. H.; Nogales, E.; Bondy-Denomy, J.; Corn, J. E.; Doudna, J. A. Sci. Adv. 2017, 12, e1701620. |
| [28] | Shen, W.; Xiong, W.; Qi, Q.; Liu, X.; Xie, Z.; Zhang, Y.; Hou, J.; Tian, T.; Zhou, X. Chin. J. Chem. 2024, 42, 1387. |
| [29] | Zhang, Y.; Zhang, Y.; Han, L.; Che, Q.; Tan, J.; Zou, P.; Chen, Y. Chin. J. Chem. 2023, 41, 3639. |
| [30] | Zhang, Y.; Wang, Q.; Wang, J.; Tang, X. ChemPlusChem 2021, 86, 587. |
| [31] | Zhang, Y.; Ling, X.; Su, X.; Zhang, S.; Wang, J.; Zhang, P.; Feng, W.; Zhu, Y. Y.; Liu, T.; Tang, X. Angew. Chem. Int. Ed. 2020, 59, 20895. |
| [32] | Wang, S.; Wei, L.; Wang, J.-Q.; Ji, H.; Xiong, W.; Liu, J.; Yin, P.; Tian, T.; Zhou, X. ACS Chem. Biol. 2020, 15, 1455. |
| [33] | Zou, R. S.; Liu, Y.; Wu, B.; Ha, T. Mol. Cell 2021, 81, 1553. |
| [34] | Sun, Y.-J.; Chen, W.-D.; Liu, J.; Li, J.-J.; Zhang, Y.; Cai, W.-Q.; Liu, L.; Tang, X.-J.; Hou, J.; Wang, M.; Cheng, L. Angew. Chem. Int. Ed. 2023, 62, e202212413. |
| [35] | Deng, H.; Xu, H.; Wang, Y.; Jia, R.; Ma, X.; Feng, Y.; Chen, H. Nucleic Acids Res. 2023, 51, 4064. |
| [36] | Tang, Y.; Pei, F.; Lu, X.; Fan, Q.; Huang, W. Adv. Opt. Mater. 2019, 7, 1900917. |
| [37] | Miao, Y.; Gu, C.; Zhu, Y.; Yu, B.; Shen, Y.; Cong, H. ChemBioChem 2018, 19, 2522. |
| [38] | Hasanzadeh, A.; Noori, H.; Jahandideh, A.; Haeri Moghaddam, N.; Kamrani Mousavi, S. M.; Nourizadeh, H.; Saeedi, S.; Karimi, M.; Hamblin, M. R. ACS Appl. Bio Mater. 2022, 5, 413. |
| [39] | Jackson, C. T.; Jeong, S.; Dorlhiac, G. F.; Landry, M. P. iScience 2021, 24, 102156. |
| [40] | Fang, T.; Cao, X.; Ibnat, M.; Chen, G. J. Nanobiotechnology 2022, 20, 354. |
| [41] | Chen, J.; Fan, T.; Xie, Z.; Zeng, Q.; Xue, P.; Zheng, T.; Chen, Y.; Luo, X.; Zhang, H. Biomaterials 2020, 237, 119827. |
| [42] | Lyu, Y.; He, S.; Li, J.; Jiang, Y.; Sun, H.; Miao, Y.; Pu, K. Angew. Chem. Int. Ed. 2019, 58, 18197. |
| [43] | Deng, S.; Li, X.; Liu, S.; Chen, J.; Li, M.; Chew, S. Y.; Leong, K. W.; Cheng, D. Sci. Adv. 2020, 6, eabb4005. |
| [44] | Yang, C.; Fu, Y.; Huang, C.; Hu, D.; Zhou, K.; Hao, Y.; Chu, B.; Yang, Y.; Qian, Z. Biomaterials 2020, 255, 120194. |
| [45] | Chen, G.; Qiu, H.; Prasad, P. N.; Chen, X. Chem. Rev. 2014, 114, 5161. |
| [46] | Dong, H.; Du, S.-R.; Zheng, X.-Y.; Lyu, G.-M.; Sun, L.-D.; Li, L.-D.; Zhang, P.-Z.; Zhang, C.; Yan, C.-H. Chem. Rev. 2015, 115, 10725. |
| [47] | Huang, J.; Li, Z.; Liu, Z. Acta Chim. Sinica 2021, 79, 1049 (in Chinese). |
| [47] | (黄菊, 李贞, 刘志洪, 化学学报, 2021, 79, 1049.) |
| [48] | Pan, Y.; Yang, J.; Luan, X.; Liu, X.; Li, X.; Yang, J.; Huang, T.; Sun, L.; Wang, Y.; Lin, Y.; Song, Y. Sci. Adv. 2019, 5, eaav7199. |
| [49] | Wang, D.; Chen, L.; Li, C.; Long, Q.; Yang, Q.; Huang, A.; Tang, H. J. Nanobiotechnology 2022, 20, 27. |
| [50] | Devarajan, A. ACS Synth. Biol. 2024, 13, 25. |
| [51] | Nihongaki, Y.; Kawano, F.; Nakajima, T.; Sato, M. Nat. Biotechnol. 2015, 33, 755. |
| [52] | Nihongaki, Y.; Yamamoto, S.; Kawano, F. Chem. Biol. 2015, 22, 169. |
| [53] | Zhou, X. X.; Zou, X.; Chung, H. K.; Gao, Y.; Liu, Y.; Qi, L. S.; Lin, M. Z. ACS Chem. Biol. 2018, 13, 443. |
| [54] | Zhou, X. X.; Fan, L. Z.; Li, P.; Shen, K.; Lin, M. Z. Science 2017, 355, 836. |
| [55] | Marino, N. D.; Pinilla Redondo, R.; Cs?rg?, B.; Bondy Denomy, J. Nat. Methods 2020, 17, 471. |
| [56] | Kim, I.; Jeong, M.; Ka, D.; Han, M.; Kim, N.-K.; Bae, E.; Suh, J.-Y. Sci. Rep. 2018, 8, 3883. |
| [57] | Zhu, Y.; Gao, A.; Zhan, Q.; Wang, Y.; Feng, H.; Liu, S.; Gao, G.; Serganov, A.; Gao, P. Mol. Cell 2019, 74, 296. |
| [58] | Harrington, L. B.; Doxzen, K. W.; Ma, E.; Liu, J. J.; Knott, G. J.; Edraki, A.; Garcia, B.; Amrani, N.; Chen, J. S.; Cofsky, J. C.; Kranzusch, P. J.; Sontheimer, E. J.; Davidson, A. R.; Maxwell, K. L.; Doudna, J. A. Cell 2017, 170, 1224. |
| [59] | Knott, G. J.; Thornton, B. W.; Lobba, M. J.; Liu, J. J.; Al Shayeb, B.; Watters, K. E.; Doudna, J. A. Nat. Struct. Mol. Biol. 2019, 26, 315. |
| [60] | León, L. M.; Park, A. E.; Borges, A. L.; Zhang, J. Y.; Bondy- Denomy, J. Nucleic Acids Res. 2021, 49, 2114. |
| [61] | Bubeck, F.; Hoffmann, M. D.; Harteveld, Z.; Aschenbrenner, S.; Bietz, A.; Waldhauer, M. C.; B?rner, K.; Fakhiri, J.; Schmelas, C.; Dietz, L.; Grimm, D.; Correia, B. E.; Eils, R.; Niopek, D. Nat. Methods 2018, 15, 924. |
| [62] | Chi, J.; Zhao, J.; Wei, S.; Li, Y.; Zhi, J.; Wang, H.; Hou, X.; Hu, L.; Zheng, X.; Gao, M. ACS Appl. Mater. Interfaces 2021, 13, 6043. |
| [63] | Yu, Y.; Wu, X.; Guan, N.; Shao, J.; Li, H.; Chen, Y.; Ping, Y.; Li, D.; Ye, H. Sci. Adv. 2020, 6, eabb1777. |
| [64] | Xu, H.; Han, P.; Qin, A.; Tang, B. Z. Acta Chim. Sinica 2023, 81, 1420 (in Chinese). |
| [64] | (徐赫, 韩鹏博, 秦安军, 唐本忠, 化学学报, 2023, 81, 1420.) |
| [65] | Jung, H. S.; Verwilst, P.; Sharma, A.; Shin, J.; Sessler, J. L.; Kim, J. S. Chem. Soc. Rev. 2018, 47, 2280. |
| [66] | Zhang, L.; Forgham, H.; Huang, X.; Shen, A.; Davis, T. P.; Qiao, R.; Guo, B. Mater. Today Adv. 2022, 14, 100226. |
| [67] | Yu, Z.; Chan, W. K.; Zhang, Y.; Tan, T. T. Y. Biomaterials 2021, 269, 120459. |
| [68] | Wang, P.; Zhang, L.; Zheng, W.; Cong, L.; Guo, Z.; Xie, Y.; Wang, L.; Tang, R.; Feng, Q.; Hamada, Y.; Gonda, K.; Hu, Z.; Wu, X.; Jiang, X. Angew. Chem. Int. Ed. 2018, 57, 1491. |
| [69] | Yin, H.; Zhou, B.; Dong, C.; Zhang, Y.; Yu, J.; Pu, Y.; Feng, W.; Sun, L.; Hu, H.; Chen, Y.; Xu, H. Adv. Funct. Mater. 2021, 31, 2107093. |
| [70] | Zhang, L.; Hou, Y.; Li, N.; Wu, K.; Zhai, J. J. Cancer Res. Clin. Oncol. 2010, 136, 1497. |
| [71] | Tao, W.; Cheng, X.; Sun, D.; Guo, Y.; Wang, N.; Ruan, J.; Hu, Y.; Zhao, M.; Zhao, T.; Feng, H.; Fan, L.; Lu, C.; Ma, Y.; Duan, J.; Zhao, M. Biomaterials 2022, 287, 121621. |
| [72] | Costa, T. E. M. M.; Raghavendra, N. M.; Penido, C. Eur. J. Med. Chem. 2020, 189, 112063. |
| [73] | Chen, X.; Chen, Y.; Xin, H.; Wan, T.; Ping, Y. Proc. Natl. Acad. Sci. 2020, 117, 2395. |
| [74] | Tang, H.; Xu, X.; Chen, Y.; Xin, H.; Wan, T.; Li, B.; Pan, H.; Li, D.; Ping, Y. Adv. Mater. 2021, 33, 2006003. |
| [75] | Liu, Z.; Shi, M.; Ren, Y.; Xu, H.; Weng, S.; Ning, W.; Ge, X.; Liu, L.; Guo, C.; Duo, M.; Li, L.; Li, J.; Han, X. Mol. Cancer. 2023, 22, 35. |
| [76] | Lin, Y. Q.; Feng, K. K.; Lu, J. Y.; Le, J. Q.; Li, W. L.; Zhang, B. C.; Li, C. L.; Song, X. H.; Tong, L. W.; Shao, J. W. J. Controlled Release 2023, 361, 727. |
| [77] | Zheng, R.; Zhang, L.; Parvin, R.; Su, L.; Chi, J.; Shi, K.; Ye, F.; Huang, X. Adv. Sci. 2023, 10, 2300195. |
| [78] | Xie, R.; Wang, Y.; Gong, S. Biomater. Sci. 2021, 9, 6012. |
| [79] | Yin, H.; Sun, L.; Pu, Y.; Yu, J.; Feng, W.; Dong, C.; Zhou, B.; Du, D.; Zhang, Y.; Chen, Y.; Xu, H. ACS Cent. Sci. 2021, 7, 2049. |
| [80] | Singh, R.; Sharma, A.; Saji, J.; Umapathi, A.; Kumar, S.; Daima, H. K. Nano Converg. 2022, 9, 21. |
| [81] | Kashyap, B. K.; Singh, V. V.; Solanki, M. K.; Kumar, A.; Ruokolainen, J.; Kesari, K. K. ACS Omega 2023, 8, 14290. |
| [82] | Li, T.; Yang, Y.; Qi, H.; Cui, W.; Zhang, L.; Fu, X.; He, X.; Liu, M.; Li, P.; Yu, T. Signal Transduct. Target. Ther. 2023, 8, 36. |
/
| 〈 |
|
〉 |
