CRISPR Technology in Tumor Immunotherapy: Application, limitations, and Improvement Methods

Authors

  • Shenghan Gao
  • Xuru Miao
  • Jiaqi Liu

DOI:

https://doi.org/10.62051/9qapmm69

Keywords:

CRISPR screen; tumor immunotherapy; off-target effect; improved method.

Abstract

The CRISPR/Cas system is a natural immune mechanism present in prokaryotes, which protects itself by specifically cutting off viral DNA that invades the bacterial body. Under the research of scientists, CRISPR technology has developed into a powerful tool in tumor immunotherapy. It can reduce the inhibitory effect of tumor microenvironment on T cells and enhance tumor immunity by specifically knocking out genes at immune checkpoints (such as PD-1/CTLA-4) on T cells cultured in vitro. However, CRISPR technology also has significant limitations, with the main limitation being its off-target effect - CRISPR is prone to mistakenly identifying and cutting off genes similar to the target gene sequence, including the normal human genome. Once the off-target effect occurs, it will destroy normal genes other than the target gene and cause irreversible damage. Through research, it has been found that CRISPR combined with other technologies can effectively avoid off target effects and reduce treatment risks. This article elaborates on the specific mechanism of CRISPR technology combined with other technologies to avoid off target effects, and explores potential improvement methods.

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References

Li, M., Sun, J., & Shi, G. Application of CRISPR screen in mechanistic studies of tumor development, tumor drug resistance, and tumor immunotherapy. Frontiers in Cell and Developmental Biology, 2023, 11.

Zhang F, Wen Y, Guo X. CRISPR/Cas9 for genome editing: progress, implications and challenges. Hum Mol Genet. 2014, Sep 15; 23 (R1): R40 - 6.

Stadtmauer EA, et al. CRISPR-engineered T cells in patients with refractory cancer. Science. 2020, Feb 28; 367 (6481): eaba7365.

Razeghian E, Nasution MKM, Rahman HS, et al. A deep insight into CRISPR/Cas9 application in CAR-T cell-based tumor immunotherapies. Stem Cell Res Ther. 2021, Jul 28; 12 (1): 428.

Wei W, Chen ZN, Wang K. CRISPR/Cas9: A Powerful Strategy to Improve CAR-T Cell Persistence. Int J Mol Sci. 2023, Aug 1; 24 (15): 12317.

Wu HY, Cao CY. The application of CRISPR-Cas9 genome editing tool in cancer immunotherapy. Brief Funct Genomics. 2019, Mar 22; 18 (2): 129 - 132.

Wang SW, Gao C, Zheng YM, Yi L, Lu JC, Huang XY, Cai JB, Zhang PF, Cui YH, Ke AW. Current applications and future perspective of CRISPR/Cas9 gene editing in cancer. Mol Cancer. 2022, Feb 21; 21 (1): 57.

Manghwar H, Li B, Ding X, Hussain A, Lindsey K, Zhang X, Jin S. CRISPR/Cas Systems in Genome Editing: Methodologies and Tools for sgRNA Design, Off-Target Evaluation, and Strategies to Mitigate Off-Target Effects. Adv Sci (Weinh). 2020, Feb 6; 7 (6): 1902312.

Klein, B. Eslami-Mossallam, D.G. Arroyo, M. Depken. Hybridization kinetics explains CRISPR-cas off-targeting rules. Cell Rep, 22 2018, pp. 1413 - 1423.

Donohoue PD, Pacesa M, Lau E, et al. Conformational control of Cas9 by CRISPR hybrid RNA-DNA guides mitigates off-target activity in T cells. Mol Cell. 2021, Sep 2; 81 (17): 3637 - 3649.e5.

Bravo JPK, Liu MS, Hibshman GN, et al. Structural basis for mismatch surveillance by CRISPR-Cas9. Nature. 2022, Mar; 603 (7900): 343 - 347.

Kulcsár, P.I., Tálas, A., Ligeti, Z. et al. SuperFi-Cas9 exhibits remarkable fidelity but severely reduced activity yet works effectively with ABE8e. 2022, Nat Commun 13, 6858.

Harrington LB, Doxzen KW, Ma E, et al. A Broad-Spectrum Inhibitor of CRISPR-Cas9. Cell. 2017, Sep 7; 170 (6): 1224 - 1233.e15.

Dong, D., Guo, M., Wang, S. et al. Structural basis of CRISPR–SpyCas9 inhibition by an anti-CRISPR protein. Nature 2017, 546, 436 – 439.

Jiyung Shin et al. Disabling Cas9 by an anti-CRISPR DNA mimic.Sci. Adv. 2017, 3, e1701620.

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Published

24-03-2024

How to Cite

Gao, S., Miao, X., & Liu, J. (2024). CRISPR Technology in Tumor Immunotherapy: Application, limitations, and Improvement Methods. Transactions on Materials, Biotechnology and Life Sciences, 3, 587-593. https://doi.org/10.62051/9qapmm69