CRISPR in Cancer Biology and Bovine Viral Diarrhea Therapy: Precision Genome Editing at the Frontier of Oncology and Viral Pathogenesis
DOI:
https://doi.org/10.71320/bcs.0005Keywords:
CRISPR, precision oncology, cancer therapy, synthetic lethality, genome editingAbstract
CRISPR has become a revolutionary tool for cancer biology and therapy with unprecedented precision for genome editing. Besides cancer, CRISPR is also under research for possible use in the treatment of viral diseases, such as Bovine Viral Diarrhea Virus (BVDV), a serious livestock problem. Through enabling gene modifications to be made to individual genes, CRISPR is used in identifying oncogenic drivers, characterizing tumor suppressor networks, and designing innovative therapeutics. This review focuses on the various uses of CRISPR for cancer studies with special attention to methods like gene knockout, gene activation, and base editing that each has a great potential for correcting oncogenic mutations and restoring tumor suppressor activity. Moreover, CRISPR's capacity to regulate viral replication, as that of BVDV, signifies its dual role in oncology as well as in viral pathogenesis. Interventions based on CRISPR such as chimeric antigen receptor (CAR) T cell therapy and synthetic lethality are essentially revolutionizing cancer therapy by improving immune responses and capitalizing on the specificity that is characteristic of cancer cells. However, off-target effects, tumor heterogeneity, and ethical dilemmas remain onerous challenges for clinical application. CRISPR delivery systems, despite playing a central role in advancing cancer therapies, also have prospects in optimizing the effectiveness of treatment against viral pathogens like BVDV. Advances in delivery systems using nanoparticles and viral vectors are mitigating against these challenges and improving efficacy and specificity of CRISPR reagent in vivo. In addition to this, continued progress in new technologies such as prime editing and base editing is predicted to improve precision and efficacy of CRISPR-based therapy. Since CRISPR technology is continuously developing, CRISPR's potential to treat both cancer and viral infections, like BVDV, simultaneously will be instrumental in precision medicine. This review highlights the revolutionary potential of CRISPR to revolutionize cancer treatment paradigms and brings hope for more effective and individualized therapy. With potential developments to emergent and potentiated CRISPR tools and reagents, it is predicted that they will play a center stage role in precision oncology and promote better patient results.
References
Abdussadyk, D., & Beisenova, A. (2023). The prospects and challenges of CRISPR/Cas9 gene editing in cancer therapy: A literature review. Oncologia I Radiologia Kazakhstana, 68(2), 64–68. https://doi.org/10.52532/2663-4864-2023-2-68-64-68 DOI: https://doi.org/10.52532/2663-4864-2023-2-68-64-68
Anirudh, K., Jasti, T., & Kandra, P. (2021). CRISPR/Cas9 in cancer: An attempt to the present trends and future prospects. Biotechnology and Applied Biochemistry, 69(3), 1238–1251. https://doi.org/10.1002/bab.2200 DOI: https://doi.org/10.1002/bab.2200
Ashworth, A., & Lord, C. (2018). Synthetic lethal therapies for cancer: What's next after PARP inhibitors? Nature Reviews Clinical Oncology, 15(9), 564–576. https://doi.org/10.1038/s41571-018-0055-6 DOI: https://doi.org/10.1038/s41571-018-0055-6
Banerjee, A., Malonia, S., & Dutta, S. (2021). Frontiers of CRISPR-Cas9 for cancer research and therapy. Journal of Exploratory Research in Pharmacology. https://doi.org/10.14218/jerp.2020.00033 DOI: https://doi.org/10.14218/JERP.2020.00033
Brokowski, C., & Adli, M. (2019). CRISPR ethics: Moral considerations for applications of a powerful tool. Journal of Molecular Biology, 431(1), 88–101. https://doi.org/10.1016/j.jmb.2018.05.044 DOI: https://doi.org/10.1016/j.jmb.2018.05.044
Chandran, S. S., & Klebanoff, C. A. (2019). T cell receptor-based cancer immunotherapy: Emerging efficacy and pathways of resistance. Immunological Reviews, 290(1), 127–147. https://doi.org/10.1111/imr.12772 DOI: https://doi.org/10.1111/imr.12772
Chen, S., Sanjana, N., Zheng, K., Shalem, O., Lee, K., Shi, X., ... & Sharp, P. (2015). Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis. Cell, 160(6), 1246–1260. https://doi.org/10.1016/j.cell.2015.02.038 DOI: https://doi.org/10.1016/j.cell.2015.02.038
Dai, M., Yan, G., Wang, N., Daliah, G., Edick, A., Poulet, S., ... & Lebrun, J. (2021). In vivo genome-wide CRISPR screen reveals breast cancer vulnerabilities and synergistic mTOR/Hippo targeted combination therapy. Nature Communications, 12(1), Article 2935. https://doi.org/10.1038/s41467-021-23316-4 DOI: https://doi.org/10.1038/s41467-021-23316-4
Deng, X. (2023). Progress in the application of gene editing technology in cancer treatments – taking CRISPR as an example. Theoretical and Natural Science, 27(1), 92–95. https://doi.org/10.54254/2753-8818/27/20240708 DOI: https://doi.org/10.54254/2753-8818/27/20240708
Finn, J., Smith, A., Patel, M., Shaw, L., Youniss, M., van Heteren, J., ... & Morrissey, D. (2018). A single administration of CRISPR/Cas9 lipid nanoparticles achieves robust and persistent in vivo genome editing. Cell Reports, 22(9), 2227–2235. https://doi.org/10.1016/j.celrep.2018.02.014 DOI: https://doi.org/10.1016/j.celrep.2018.02.014
Huang, C., Lee, K., & Doudna, J. (2018). Applications of CRISPR-Cas enzymes in cancer therapeutics and detection. Trends in Cancer, 4(7), 499–512. https://doi.org/10.1016/j.trecan.2018.05.006 DOI: https://doi.org/10.1016/j.trecan.2018.05.006
Kleinstiver, B., Pattanayak, V., Prew, M., Tsai, S., Nguyen, N., Zheng, Z., ... & Joung, J. (2016). High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature, 529(7587), 490–495. https://doi.org/10.1038/nature16526 DOI: https://doi.org/10.1038/nature16526
Knott, G., & Doudna, J. (2018). CRISPR-Cas guides the future of genetic engineering. Science, 361(6405), 866–869. https://doi.org/10.1126/science.aat5011 DOI: https://doi.org/10.1126/science.aat5011
Lee, H., Kim, H., & Lee, S. (2020). CRISPR-Cas9-mediated pinpoint microbial genome editing aided by target-mismatched sgRNAs. Genome Research, 30(5), 768–775. https://doi.org/10.1101/gr.257493.119 DOI: https://doi.org/10.1101/gr.257493.119
Legut, M., Dolton, G., Mian, A., Ottmann, O., & Sewell, A. (2018). CRISPR-mediated TCR replacement generates superior anticancer transgenic T cells. Blood, 131(3), 311–322. https://doi.org/10.1182/blood-2017-05-787598 DOI: https://doi.org/10.1182/blood-2017-05-787598
Liu, Q., Zhao, K., Wang, C., Zhang, Z., Zheng, C., Zhao, Y., ... & Liu, Y. (2018). Multistage delivery nanoparticle facilitates efficient CRISPR/dCas9 activation and tumor growth suppression in vivo. Advanced Science, 6(1), Article 1801423. https://doi.org/10.1002/advs.201801423 DOI: https://doi.org/10.1002/advs.201801423
Marusyk, A., & Polyak, K. (2010). Tumor heterogeneity: Causes and consequences. Biochimica et Biophysica Acta, 1805(1), 105–117. https://doi.org/10.1016/j.bbcan.2009.11.002 DOI: https://doi.org/10.1016/j.bbcan.2009.11.002
Mondal, R., Brahmbhatt, N., Sandhu, S., Shah, H., Vashi, M., Gandhi, S., ... & Patel, P. (2023). Applications of CRISPR as a genetic scalpel for the treatment of cancer: A translational narrative review. Cureus, 15(2), Article e50031. https://doi.org/10.7759/cureus.50031 DOI: https://doi.org/10.7759/cureus.50031
Nüssing, S., House, I., Kearney, C., Vervoort, S., Beavis, P., Oliaro, J., ... & Parish, I. (2020). Efficient CRISPR/Cas9 gene editing in uncultured naïve mouse T cells for in vivo studies. The Journal of Immunology, 204(8), 2308–2315. https://doi.org/10.4049/jimmunol.1901396 DOI: https://doi.org/10.4049/jimmunol.1901396
Ottaviano, G., Georgiadis, C., Gkazi, S., Syed, F., Zhan, H., Etuk, A., ... & Kim, D. (2022). Phase 1 clinical trial of CRISPR-engineered CAR19 universal T cells for treatment of children with refractory B cell leukemia. Science Translational Medicine, 14(668), eabq3010. https://doi.org/10.1126/scitranslmed.abq3010 DOI: https://doi.org/10.1126/scitranslmed.abq3010
Rousset, F., Cui, L., Siouve, E., Bécavin, C., Depardieu, F., & Bikard, D. (2018). Genome-wide CRISPR-dCas9 screens in E. coli identify essential genes and phage host factors. PLoS Genetics, 14(11), e1007749. https://doi.org/10.1371/journal.pgen.1007749 DOI: https://doi.org/10.1371/journal.pgen.1007749
Schmidt, R., Steinhart, Z., Layeghi, M., Freimer, J., Bueno, R., Nguyen, V., ... & Marson, A. (2022). CRISPR activation and interference screens decode stimulation responses in primary human T cells. Science, 375(6580), eabj4008. https://doi.org/10.1126/science.abj4008 DOI: https://doi.org/10.1126/science.abj4008
Shi, X., Kitano, A., Jiang, Y., Luu, V., Hoegenauer, K., & Nakada, D. (2018). Clonal expansion and myeloid leukemia progression modeled by multiplex gene editing of murine hematopoietic progenitor cells. Experimental Hematology, 64, 33–44.e5. https://doi.org/10.1016/j.exphem.2018.04.009 DOI: https://doi.org/10.1016/j.exphem.2018.04.009
Sioson, V. A., Kim, M., & Joo, J. (2021). Challenges in delivery systems for CRISPR-based genome editing and opportunities of nanomedicine. Biomedical Engineering Letters, 11(3), 217–233. https://doi.org/10.1007/s13534-021-00199-4 DOI: https://doi.org/10.1007/s13534-021-00199-4
Stadtmauer, E., Fraietta, J., Davis, M., Cohen, A., Weber, K., Lancaster, E., ... & June, C. (2020). CRISPR-engineered T cells in patients with refractory cancer. Science, 367(6481), eaba7365. https://doi.org/10.1126/science.aba7365 DOI: https://doi.org/10.1126/science.aba7365
Sun, W., Wang, J., Hu, Q., Zhou, X., Khademhosseini, A., & Gu, Z. (2020). CRISPR-Cas12a delivery by DNA-mediated bioresponsive editing for cholesterol regulation. Science Advances, 6(21), eaba2983. https://doi.org/10.1126/sciadv.aba2983 DOI: https://doi.org/10.1126/sciadv.aba2983
Tesařík, J., Mendoza‐Tesarik, R., & Mendoza, C. (2018). Would human preimplantation gene therapy based on CRISPR-Cas9 genome editing increase cancer risk in the offspring? Gynecology & Reproductive Health, 2(5), Article 1056. https://doi.org/10.33425/2639-9342.1056 DOI: https://doi.org/10.33425/2639-9342.1056
Tian, X., Gu, T., Patel, S., Bode, A., Lee, M., & Dong, Z. (2019). CRISPR/Cas9-An evolving biological tool kit for cancer biology and oncology. NPJ Precision Oncology, 3(1), Article 8. https://doi.org/10.1038/s41698-019-0080-7 DOI: https://doi.org/10.1038/s41698-019-0080-7
Toledo, C., Ding, Y., Hoellerbauer, P., Davis, R., Basom, R., Girard, E., ... & Paddison, P. (2015). Genome-wide CRISPR-Cas9 screens reveal loss of redundancy between PKMYT1 and WEE1 in glioblastoma stem-like cells. Cell Reports, 13(11), 2425–2439. https://doi.org/10.1016/j.celrep.2015.11.021 DOI: https://doi.org/10.1016/j.celrep.2015.11.021
Wang, P., Zhang, L., Zheng, W., Cong, L., Guo, Z., Xie, Y., ... & Jiang, X. (2018). Thermo-triggered release of CRISPR-Cas9 system by lipid-encapsulated gold nanoparticles for tumor therapy. Angewandte Chemie, 57(6), 1491–1496. https://doi.org/10.1002/anie.201708689 DOI: https://doi.org/10.1002/anie.201708689
Xia, A., He, Q., Wang, J., Zhu, J., Sha, Y., Sun, B., ... & Lu, X. (2018). Applications and advances of CRISPR-Cas9 in cancer immunotherapy. Journal of Medical Genetics, 56(1), 4–9. https://doi.org/10.1136/jmedgenet-2018-105422 DOI: https://doi.org/10.1136/jmedgenet-2018-105422
Yang, Y., Xu, J., Ge, S., & Lai, L. (2021). CRISPR/Cas: Advances, limitations, and applications for precision cancer research. Frontiers in Medicine, 8, 649896. https://doi.org/10.3389/fmed.2021.649896 DOI: https://doi.org/10.3389/fmed.2021.649896
Yang, F., Aliyari, S., Zhu, Z., Zheng, H., Cheng, G., & Zhang, S. (2025). CRISPR-Cas: A game-changer in vaccine development and the fight against viral infections. Trends in Microbiology. DOI: https://doi.org/10.1016/j.tim.2025.02.006
Yao, R., Xu, Y., Wang, L., Wang, D., Ren, L., Ren, C., Li, C., Li, X., Ni, W., He, Y., Hu, R., Guo, T., Li, Y., Li, L., Wang, X., & Hu, S. (2021). CRISPR-Cas13a-based detection for bovine viral diarrhea virus. Frontiers in Veterinary Science, 8, 603919. https://doi.org/10.3389/fvets.2021.603919 DOI: https://doi.org/10.3389/fvets.2021.603919
Zhang, B., Luo, B., Zou, J., Wu, P., Jiang, J., Le, J., ... & Shao, J. (2020). Co-delivery of sorafenib and CRISPR/Cas9 based on targeted core-shell hollow mesoporous organosilica nanoparticles for synergistic HCC therapy. ACS Applied Materials & Interfaces, 12(51), 57362–57372. https://doi.org/10.1021/acsami.0c17660 DOI: https://doi.org/10.1021/acsami.0c17660
Zhang, C., Wang, X., Liu, G., Ren, H., Liu, J., Jiang, Z., ... & Zhang, Y. (2023). CRISPR/Cas9 and chlorophyll coordination micelles for cancer treatment by genome editing and photodynamic therapy. Small, 19(17), 2206981. https://doi.org/10.1002/smll.202206981 DOI: https://doi.org/10.1002/smll.202206981
Zhang, D., Wang, G., Yu, X., Wei, T., Farbiak, L., Johnson, L., ... & Siegwart, D. (2022). Enhancing CRISPR/Cas gene editing through modulating cellular mechanical properties for cancer therapy. Nature Physics, 17(7), 777–787. https://doi.org/10.1038/s41565-022-01122-3 DOI: https://doi.org/10.1038/s41565-022-01122-3
Zhao, M., Cheng, X., Shao, P., Yao, D., Wu, Y., Xiao, L., ... & Zhang, J. (2024). Bacterial protoplast-derived nanovesicles carrying CRISPR-Cas9 tools re-educate tumor-associated macrophages for enhanced cancer immunotherapy. Nature Communications, 15(1), Article 44941. https://doi.org/10.1038/s41467-024-44941-9 DOI: https://doi.org/10.1038/s41467-024-44941-9
Zhen, S., Liu, Y., Lu, J., Tuo, X., Yang, X., Chen, H., ... & Li, X. (2020). Human papillomavirus oncogene manipulation using clustered regularly interspersed short palindromic repeats/Cas9 delivered by pH-sensitive cationic liposomes. Human Gene Therapy, 31(5–6), 309–324. https://doi.org/10.1089/hum.2019.312 DOI: https://doi.org/10.1089/hum.2019.312

Published
Data Availability Statement
Not applicable
License
Copyright (c) 2025 Bio Communications

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Copyright © Bio Communications. This article is published under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. Under this license, you are free to share (copy and redistribute) this material in any medium or format for non-commercial purposes, provided you give appropriate credit to the author(s) and the journal. No modifications or adaptations of the material are permitted. The copyright for this article remains with the journal Bio Communications.