Recent Advances in CRISPR/Cas9-Mediated Disease Modeling

Abstract

Promising advances in cellular and animal models for severe diseases have been demonstrated by recent improvements in the field of gene editing techniques. The CRISPR/Cas9 technique is covered in length in this overview, with an emphasis on its most recent uses in the development of cellular and human disease models. The importance of these models in comprehending the underlying mechanisms of sickness and creating possible treatments is highlighted. The prospects and potential uses of CRISPR/Cas9 technology in the field of biomedicine are also discussed. The value of disease modeling in expanding the understanding of illness pathophysiology and in creating new treatment approaches is highlighted. The aim of this study is to provide a thorough analysis of the present and future applications of CRISPR/Cas9 in disease modeling and treatment development.

Keywords

• CRISPR/Cas9
• cellular models
• animal models

CRISPR/Cas9 Aracılı Hastalık Modellemesindeki Son Gelişmeler

Öz

Ölümcül hastalıklar için hücresel ve hayvan modellerindeki umut verici gelişmeler, gen düzenleme tekniklerindeki son iyileştirmeler tarafından gösterilmiştir. Bu derlemede, CRISPR/Cas9 tekniği kapsamlı bir şekilde ele alınmış ve özellikle hücresel ve insan hastalık modellerinin geliştirilmesindeki en son kullanımları vurgulanmıştır. Bu modellerin hastalıkların altındaki mekanizmaları anlamak ve olası tedaviler geliştirmek üzerindeki önemi tartışılmaktadır. Ayrıca, CRISPR/Cas9 teknolojisinin biyomedikal alandaki potansiyel kullanımları ve gelecekteki potansiyelleri de incelenmektedir. Hastalık modellemenin hastalık patofizyolojisi anlamaya ve yeni tedavi yaklaşımları geliştirmeye katkısının değerine dair bir tartışma da yer almaktadır. Bu çalışmanın amacı, CRISPR/Cas9'un hastalık modelleme ve tedavi geliştirme alanındaki mevcut ve gelecekteki uygulamalarını kapsamlı bir şekilde sunmaktır.

Anahtar Kelimeler

• CRISPR/Cas9
• hücresel modeller
• hayvan modelleri

References

1. 1. Yun Y, Ha Y. CRISPR/Cas9-mediated gene correction to understand ALS. Int J Mol Sci. 2020;21(11):3801.
2. 2. Li H, Yang Y, Hong W, Huang M, Wu M, Zhao X. Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects. Signal Transduct Target Ther. 2020;5(1):1.
3. 3. Görücü Yilmaz S. Genome editing technologies: CRISPR, LEAPER, RESTORE, ARCUT, SATI, and RESCUE. Excli J. 2021;20:19-45.
4. 4. Asmamaw M, Zawdie B. Mechanism and applications of CRISPR/Cas-9-mediated genome editing. Biologics. 2021;15:353-361.
5. 5. Kick L, Kirchner M, Schneider S. CRISPR-Cas9: From a bacterial immune system to genome-edited human cells in clinical trials. Bioengineered. 2017;8(3):280-286.
6. 6. Ibrahim AU, Özsöz M, Saeed Z, Tirah G, Gideon O. Genome engineering using the CRISPR Cas9 system. Biomed Pharm Sci. 2019;2(2):1–7.
7. 7. Leon LM, Mendoza SD, Bondy-Denomy J. How bacteria control the CRISPR-Cas arsenal. Curr Opin Microbiol. 2018;42:87-95.
8. 8. Du Y, Liu Y, Hu J, Peng X, Liu Z. CRISPR/Cas9 systems: Delivery technologies and biomedical applications. Asian J Pharm Sci. 2023;18(6):100854.

9. 9. Xu Y, Li Z. CRISPR-Cas systems: Overview, innovations and applications in human disease research and gene therapy. Comput Struct Biotechnol J. 2020;18:2401-2415.
10. 10. Xue C, Sashital DG. Mechanisms of type I-E and I-F CRISPR-Cas systems in enterobacteriaceae. EcoSal Plus. 2019;8(2):10.1128/ecosalplus.ESP-0008-2018.
11. 11. Chylinski K, Le Rhun A, Charpentier E. The tracrRNA and Cas9 families of type II CRISPR-Cas immunity systems. RNA Biol. 2013;10(5):726-37.
12. 12. Liao C, Beisel CL. The tracrRNA in CRISPR Biology and Technologies. Annu Rev Genet. 2021;55:161-181.
13. 13. Provasek VE, Mitra J, Malojirao VH, Hegde ML. DNA double-strand breaks as pathogenic lesions in neurological disorders. Int J Mol Sci. 2022;23(9):4653.
14. 14. Wang RC, Wang Z. Precision medicine: disease subtyping and tailored treatment. Cancers (Basel). 2023;15(15):3837.
15. 15. Storey J, Gobbetti T, Olzinski A, Berridge BR. A Structured approach to optimizing animal model selection for human translation: the animal model quality assessment. Ilar J. 2021;62(1-2):66-76.
16. 16. Bhardwaj A, Nain V. TALENs-an indispensable tool in the era of CRISPR: a mini review. J Genet Eng Biotechnol. 2021;19(1):125.
17. 17. Vermilyea SC, Babinski A, Tran N, et al. In Vitro CRISPR/Cas9-directed gene editing to model LRRK2 G2019S Parkinson's Disease in common marmosets. Sci Rep. 2020;10(1):3447.
18. 18. Li P, Xi Y, Zhang Y, et al. GLA mutations suppress autophagy and stimulate lysosome generation in fabry disease. Cells. 2024;13(5):437.
19. 19. Cui S, Shin YJ, Fang X, et al. CRISPR/Cas9-mediated A4GALT suppression rescues Fabry disease phenotypes in a kidney organoid model. Transl Res. 2023;258:35-46.
20. 20. Komori T. Functions of osteocalcin in bone, pancreas, testis, and muscle. Int J Mol Sci. 2020;21(20):7513.
21. 21. Lambert LJ, Challa AK, Niu A, et al. Increased trabecular bone and improved biomechanics in an osteocalcin-null rat model created by CRISPR/Cas9 technology. Dis Model Mech. 2016;9(10):1169–1179.
22. 22. Teame T, Zhang Z, Ran C, et al. The use of zebrafish (Danio rerio) as biomedical models. Anim Front. 2019;9(3):68-77.
23. 23. Chahardehi AM, Arsad H, Lim V. Zebrafish as a successful animal model for screening toxicity of medicinal plants. Plants (Basel). 2020;9(10):1345.
24. 24. Liu J, Zhou Y, Qi X, et al. CRISPR/Cas9 in zebrafish: an efficient combination for human genetic diseases modeling. Hum Genet. 2017;136(1):1-12.
25. 25. Hwang WY, Fu Y, Reyon D, et al. Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol. 2013;31(3):227-9.
26. 26. Gil-Martínez J, Macias I, Unione L, et al. Therapeutic targeting of fumaryl acetoacetate hydrolase in hereditary tyrosinemia type I. Int J Mol Sci. 2021;22(4):1789.
27. 27. Gu P, Yang Q, Chen B, et al. Genetically blocking HPD via CRISPR-Cas9 protects against lethal liver injury in a pig model of tyrosinemia type I. Mol Ther Methods Clin Dev. 2021;21:530-547.
28. 28. Javaid D, Ganie SY, Hajam YA, Reshi MS. CRISPR/Cas9 system: a reliable and facile genome editing tool in modern biology. Mol Biol Rep. 2022;49(12):12133-12150.
29. 29. Nasrallah A, Sulpice E, Kobaisi F, Gidrol X, Rachidi W. CRISPR-Cas9 technology for the creation of biological avatars capable of modeling and treating pathologies: from discovery to the latest improvements. Cells. 2022;11(22):3615.
30. 30. Israr J, Kumar A. Current progress in CRISPR-Cas systems for rare diseases. Prog Mol Biol Transl Sci. 2025;210:163-203. doi: 10.1016/bs.pmbts.2024.07.019.