Biorthogonal combined gene editing technology being applied to tumor treatment

Hanyue Wei

doi:10.54097/27g2qs84

Authors

Hanyue Wei

DOI:

https://doi.org/10.54097/27g2qs84

Keywords:

tumor treatment, biological orthogonal technology, gene editing technology, protein anchoring, T cell epitopes, modular platforms.

Abstract

Because of the special complexity of tumor treatment, it has been a hot topic in medical research for a long time. Although CRISPR system assisted immunotherapy has been shown to be a good option, it still lacks the defect of targeting. The discovery of biological orthogonal reaction provides a new method for attenuating and enhancing the efficacy of tumor immunotherapy. In this paper, biological orthogonal reaction is introduced, and the application of biological orthogonal technology and gene editing technology in tumor therapy is studied. The study confirmed that biological orthogonal response can be used as an assistant to enhance the efficacy of gene editing technology mediated tumor targeted therapy and reduce the side effects, which provides a new idea and method for tumor therapy. Because of its high stability as well as extremely fast reaction rate, the newly discovered pentavariant diheterocyclic monosubstituted tetrazine can be considered in combination with gene editing technology for protein anchoring, controllable activation of T cell epitopes, construction of modular platforms or participation in the regulation of base editors in the future to achieve the purpose of tumor treatment.

Downloads

Download data is not yet available.

References

[1] Blackman, M. L., Royzen, M., & Fox, J. M. 2008. Tetrazine ligation: fast bioconjugation based on in-verse-electron-demand Diels− Alder reactivity. Journal of the American Chemical Society, 130 (41), 13518 - 13519.

[2] Devaraj, N. K., Weissleder, R., & Hilderbrand, S. A. 2008. Tetrazine-based cycloadditions: application to pretargeted live cell imaging. Bioconjugate chemistry, 19 (12), 2297 - 2299.

[3] Hao, M., Hou, S., Li, W., Li, K., Xue, L., Hu, Q., ... & Zhang, C. 2020. Combination of metabolic in-tervention and T cell therapy enhances solid tumor immunotherapy. Science translational medi-cine, 12 (571), eaaz6667.

[4] Ji, X., Pan, Z., Yu, B., De La Cruz, L. K., Zheng, Y., Ke, B., & Wang, B. 2019. Click and release: bioorthogonal approaches to “on-demand” activation of prodrugs. Chemical Society Reviews, 48(4), 1077-1094.Streu, C.; Meggers, E. Angew. Chem., Int. Ed. 2006, 45, 5645.

[5] Kislukhin, A. A., Hong, V. P., Breitenkamp, K. E., & Finn, M. G. 2013. Relative performance of al-kynes in copper-catalyzed azide–alkyne cycloaddition. Bioconjugate chemistry, 24(4), 684-689.

[6] Li, Y., Su, Y., Wang, H., Xie, Y., Wang, X., Chang, L., ... & Liu, T. 2024. Computation-Guided Dis-covery of Diazole Monosubstituted Tetrazines as Optimal Bioorthogonal Tools. Journal of the Amer-ican Chemical Society, 146 (39), 26884 - 26896.

[7] Ngai, W. S. C., Yang, S., Zeng, X., Liu, Y., Lin, F., Wang, X., ... & Chen, P. R. 2022. Bioorthogonally activatable base editing for on-demand pyroptosis. Journal of the American Chemical Socie-ty, 144 (12), 5411 - 5417.

[8] Pérez‐López, A. M., Rubio‐Ruiz, B., Sebastián, V., Hamilton, L., Adam, C., Bray, T. L., ... & Unciti‐Broceta, A. 2017. Gold‐triggered uncaging chemistry in living systems. Angewandte Chemie Inter-national Edition, 56 (41), 12548 - 12552.

[9] Qu, G., Li, A., Acevedo‐Rocha, C. G., Sun, Z., & Reetz, M. T. 2020. The crucial role of methodology development in directed evolution of selective enzymes. Angewandte Chemie International Edi-tion, 59 (32), 13204 - 13231.

[10] Saxon, E., & Bertozzi, C. R. 2000. Cell surface engineering by a modified Staudinger reac-tion. Science, 287 (5460), 2007 - 2010.

[11] Streu, C., & Meggers, E. 2006. Ruthenium-induced allylcarbamate cleavage in living cells. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH-, 45 (34), 5645.

[12] Versteegen, R. M., Rossin, R., ten Hoeve, W., Janssen, H. M., & Robillard, M. S. 2013. Click to re-lease: instantaneous doxorubicin elimination upon tetrazine ligation. Angewandte Chemie Interna-tional Edition, 52 (52), 14112 - 14116.

[13] Wang, Q., Wang, Y., Ding, J., Wang, C., Zhou, X., Gao, W., ... & Liu, Z. 2020. A bioorthogonal system reveals antitumour immune function of pyroptosis. Nature, 579 (7799), 421 - 426.

[14] Wang Xin, Zhang Xianrui, Huang Zongyu, Fan Xinyuan, & Chen Peng. 2021. Research progress of bioorthogonal reactions in China. Acta Chimica Sinica, 79 (4), 406.

[15] Wang Yue, & Ye Xinshan. 2012. A rapid site-specific protein labeling method based on Diels-Alder bioorthogonal reactions. Acta Chimica Sinica, 70, 2208 - 2212.

[16] Yang, J., Yang, K., Du, S., Luo, W., Wang, C., Liu, H., ... & Song, Y. 2023. Bioorthogonal Reaction‐Mediated Tumor‐Selective Delivery of CRISPR/Cas9 System for Dual‐Targeted Cancer Immunother-apy. Angewandte Chemie, 135 (37), e202306863.

[17] Yang, S., Im, S. H., Chung, J. Y., Lee, J., Lee, K. H., Kang, Y. K., & Chung, H. J. 2024. An Antibody‐CRISPR/Cas Conjugate Platform for Target‐Specific Delivery and Gene Editing in Cancer. Advanced Science, 2308763.

[18] Zhao, Y., Dong, Y., Yang, S., Tu, Y., Wang, C., Li, J., ... & Lian, Z. 2022. Bioorthogonal equipping CAR-T cells with hyaluronidase and checkpoint blocking antibody for enhanced solid tumor immu-notherapy. ACS Central Science, 8 (5), 603 - 614.

[19] Zhang Baihong, & Yue Hongyun. 2024. The application of click chemistry in tumor research. Cancer Prevention Research, 51 (11), 951 - 955.