Abstract
The development of genome-editing technologies in 1970s has discerned a new beginning in the field of science. Out of different genome-editing approaches such as Zing-finger nucleases, TALENs, and meganucleases, clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR/Cas9) is a recent and versatile technology that has the ability of making changes to the genome of different organisms with high specificity. Cancer is a complex process that is characterized by multiple genetic and epigenetic changes resulting in abnormal cell growth and proliferation. As cancer is one of the leading causes of deaths worldwide, a large number of studies are done to understand the molecular mechanisms underlying the development of cancer. Because of its high efficiency and specificity, CRISPR/Cas9 has emerged as a novel and powerful tool in the field of cancer research. CRISPR/Cas9 has the potential to accelerate cancer research by dissecting tumorigenesis process, generating animal and cellular models, and identify drug targets for chemotherapeutic approaches. However, despite having tremendous potential, there are certain challenges associated with CRISPR/Cas9 such as safe delivery to the target, potential off-target effects and its efficacy which needs to be addressed prior to its clinical application. In this review, we give a gist of different genome-editing technologies with a special focus on CRISPR/Cas9 development, its mechanism of action and its applications, especially in different type of cancers. We also highlight the importance of CRISPR/Cas9 in generating animal models of different cancers. Finally, we present an overview of the clinical trials and discuss the challenges associated with translating CRISPR/Cas9 in clinical use.
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Abbreviations
- AAV:
-
Adeno-associated virus
- CRISPR:
-
Clustered regularly interspaced short palindromic repeats
- Cas:
-
CRISPR-associated (protein)
- ZFN:
-
Zinc finger nucleases
- TALENs:
-
Transcription activator-like effector nucleases
- crRNA:
-
CRISPR-RNA
- scaRNA:
-
Small, CRISPR–Cas-associated RNA
- sgRNA:
-
Single guide RNA
- tracrRNA:
-
Trans-activating CRISPR-RNA
- PAM:
-
Protospacer-Associated Motif
- REPAIR:
-
RNA editing for programmable A-to-I replacement
- RNP:
-
Ribonucleoprotein
- NHEJ:
-
Non-homologous end-joining
- HDR:
-
Homology Direct repair
- DSBs:
-
Double-stranded breaks
- TCR:
-
T-cell receptors
- HGT:
-
Horizontal gene transfer
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Acknowledgements
The authors gratefully acknowledge Dr. Prashanth N Suravajhala for his critical comments and suggestions. JNS acknowledges Department of Biotechnology, GOI for Ramalingaswamy re-entry fellowship awarded to him. NS gratefully acknowledges Department of Science and technology, GOI for Women Scientist fellowship (WOS-A) award.
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NaS, SG, and NiS conceived the manuscript. NaS and SG wrote the first draft with NiS. AG prepared the figures. BM helped with all the tables in the manuscript. JNS helped in the revision of the manuscript. NiS proofread the manuscript before uploading and all others agreed to the changes in the manuscript. All authors contributed to the article and approved the submitted version.
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Siva, N., Gupta, S., Gupta, A. et al. Genome-editing approaches and applications: a brief review on CRISPR technology and its role in cancer. 3 Biotech 11, 146 (2021). https://doi.org/10.1007/s13205-021-02680-4
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DOI: https://doi.org/10.1007/s13205-021-02680-4