The Emerging Role of Crispr in the Treatment of Rare Genetic Disorders

Author

Jarupla Mahika


Abstract

 Although each individual rare genetic disorder is uncommon, collectively they represent a significant global health challenge. The clustered regularly interspaced short palindromic repeats (CRISPR) genome-editing technology has attracted substantial attention in medicine due to its adaptability, simple design, high efficiency, and precision, driving rapid progress in the field. It supports scientific research by facilitating disease modelling, enhancing crop strains, and creating treatments for genetic conditions. In the medical field, it has been used or studied for disorders such as sickle cell disease and other inherited conditions. Unlike earlier gene-editing methods, it offers greater speed, lower costs, and higher precision. The technology functions by identifying specific DNA sequences using specialized proteins, allowing not just gene editing but also the control of gene expression.


Keywords

Rare genetic disorder, CRISPR, gene editing, genome, DNA, RNA, Endonucleases



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References


  1. Parthasarathy A, Raju M, Kulanthaivel L, Subbaraj GK. Introduction to Rare Genetic Disorders. InRare Genetic Disorders: Advancements in Diagnosis and Treatment 2024 May 8 (pp. 1-33). Singapore: Springer Nature Singapore.  
  1. Chu SY, Weng CY. Introduction to genetic/rare disease and the application of genetic counseling. Hu Li Za Zhi. 2017 Oct 1;64(5):11.  
  2. Anton T, Karg E, Bultmann S. Applications of the CRISPR/Cas system beyond gene editing. Biology Methods and Protocols. 2018;3(1):bpy002.
  3. O'Shea SA, Shih LC. Global epidemiology of movement disorders: rare or underdiagnosed?. InSeminars in Neurology 2023 Feb (Vol. 43, No. 01, pp. 004-016). Thieme Medical Publishers, Inc..  
  4. Eslick GD. Epidemiology of Rare Diseases. InHandbook of Epidemiology 2025 Sep 4 (pp. 1-33). New York, NY: Springer New York.
  5. Tambuyzer E, Vandendriessche B, Austin CP, Brooks PJ, Larsson K, Miller Needleman KI, Valentine J, Davies K, Groft SC, Preti R, Oprea TI. Therapies for rare diseases: therapeutic modalities, progress and challenges ahead. Nature Reviews Drug Discovery. 2020 Feb 15;19(2):93-111.  
  6. Frederiksen SD, Avramović V, Maroilley T, Lehman A, Arbour L, Tarailo-Graovac M. Rare disorders have many faces: in silico characterization of rare disorder spectrum. Orphanet Journal of Rare Diseases. 2022 Feb 22;17(1):76.  
  7. Pogue RE, Cavalcanti DP, Shanker S, Andrade RV, Aguiar LR, de Carvalho JL, Costa FF. Rare genetic diseases: update on diagnosis, treatment and online resources. Drug discovery today. 2018 Jan 1;23(1):187-95.    
  8. Zebanaz A, Kareem AM, Aher AA, Thitame SN. Personalized medicine in treating rare genetic disorders: a review. Journal of Pharmacy and Bioallied Sciences. 2025 May 1;17(Suppl 1):S59-62.
  9. Xu Y, Li Z. CRISPR-Cas systems: Overview, innovations and applications in human disease research and gene therapy. Computational and structural biotechnology journal. 2020 Jan 1;18:2401-15.
  10. Wang JY, Doudna JA. CRISPR technology: A decade of genome editing is only the beginning. Science. 2023 Jan 20;379(6629):eadd8643.
  11. Jiang F, Doudna JA. CRISPR–Cas9 structures and mechanisms. Annual review of biophysics. 2017 May 22;46:505-29.
  12. Asmamaw M, Zawdie B. Mechanism and applications of CRISPR/Cas-9-mediated genome editing. Biologics: targets and therapy. 2021 Aug 21:353-61.
  13. Mitra S, Anand U, Ghorai M, Kant N, Kumar M, Radha N, Jha NK, Swamy MK, Proćków J, de la Lastra JM, Dey A. Genome editing technologies, mechanisms and improved production of therapeutic phytochemicals: Opportunities and prospects. Biotechnology and Bioengineering. 2023 Jan;120(1):82-94.
  14. Doughty K, Baldock RA. DNA repair and gene editing: the director’s cut. The Biochemist. 2021 Dec 23;43(6):16-20.
  15. Xu Y, Li Z. CRISPR-Cas systems: Overview, innovations and applications in human disease research and gene therapy. Computational and structural biotechnology journal. 2020 Jan 1;18:2401-15.
  16. Agha AS, Al-Samydai A, Aburjai T. New frontiers in CRISPR: Addressing antimicrobial resistance with Cas9, Cas12, Cas13, and Cas14. Heliyon. 2025 Jan 30;11(2).
  17. Agha AS, Al-Samydai A, Aburjai T. New frontiers in CRISPR: Addressing antimicrobial resistance with Cas9, Cas12, Cas13, and Cas14. Heliyon. 2025 Jan 30;11(2
  18. Gaj T. Next-generation CRISPR technologies and their applications in gene and cell therapy. Trends in biotechnology. 2021 Jul 1;39(7):692-705.
  19. Thomson T, Li G, Strilchuk A, Cui H, Wang B, Li B. Harnessing artificial intelligence to advance CRISPR-based genome editing technologies. Nature Reviews Genetics. 2026 Mar;27(3):212-30.
  20. Hilton IB, D'ippolito AM, Vockley CM, Thakore PI, Crawford GE, Reddy TE, Gersbach CA. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nature biotechnology. 2015 May;33(5):510-7.
  21. Maeder ML, Linder SJ, Cascio VM, Fu Y, Ho QH, Joung JK. CRISPR RNA–guided activation of endogenous human genes. Nature methods. 2013 Oct;10(10):977-9
  22. Larson MH, Gilbert LA, Wang X, Lim WA, Weissman JS, Qi LS. CRISPR interference (CRISPRi) for sequence-specific control of gene expression. Nature protocols. 2013 Nov;8(11):2180-96.
  23. Esoh K, Wonkam A. Evolutionary history of sickle-cell mutation: implications for global genetic medicine. Human molecular genetics. 2021 Mar 1;30(R1):R119-28
  24. Mangla A, Agarwal N, Maruvada S. Sickle cell anemia. InStatPearls [Internet] 2023 Sep 4. StatPearls Publishing.
  25. Galanello R, Origa R. Beta-thalassemia. Orphanet journal of rare diseases. 2010 May 21;5(1):11.
  26. Hu J, Zhong Y, Xu P, Xin L, Zhu X, Jiang X, Gao W, Yang B, Chen Y. β-Thalassemia gene editing therapy: Advancements and difficulties. Medicine. 2024 May 3;103(18):e38036.  
  27. Dwight M, Marshall B. CFTR modulators: transformative therapies for cystic fibrosis. Journal of managed care & specialty pharmacy. 2021 Feb;27(2):281-4.
  28. Plasschaert LW, MacDonald KD, Moffit JS. Current landscape of cystic fibrosis gene therapy. Frontiers in pharmacology. 2024 Oct 8;15:1476331.  
  29. Alkanli SS, Alkanli N, Ay A, Albeniz I. CRISPR/Cas9 mediated therapeutic approach in Huntington’s disease. Molecular Neurobiology. 2023 Mar;60(3):1486-98.   
  30. Perrault I, Rozet JM, Gerber S, Ghazi I, Leowski C, Ducroq D, Souied E, Dufier JL, Munnich A, Kaplan J. Leber congenital amaurosis. Molecular genetics and metabolism. 1999 Oct 1;68(2):200-8.
  31. Ruan GX, Barry E, Yu D, Lukason M, Cheng SH, Scaria A. CRISPR/Cas9-mediated genome editing as a therapeutic approach for Leber congenital amaurosis 10. Molecular therapy. 2017 Feb 1;25(2):331-41.
  32. Mullard A. First in vivo CRISPR candidate enters the clinic. Nature Reviews Drug Discovery. 2019 Sep 1;18(9):656-7.
  33. Bagby GC, Alter BP. Fanconi anemia. InSeminars in hematology 2006 Jul 1 (Vol. 43, No. 3, pp. 147-156). WB Saunders.
  34. Geng J, Wang X, Pan J, Khan D, Pimcharoen S, Zhang Y, Mosammaparast N, Hirose S, Petrucelli L, Brandman O, Qi LS. CRISPR activation of the ribosome-associated quality control factor ASCC3 ameliorates fragile X syndrome phenotypes in mice. Science translational medicine. 2025 Oct 8;17(819):eadq3551.
  35. Palmieri M, Pozzer D, Landsberger N. Advanced genetic therapies for the treatment of Rett syndrome: state of the art and future perspectives. Frontiers in Neuroscience. 2023 May 25;17:1172805.
  36. Xu CL, Ruan MZ, Mahajan VB, Tsang SH. Viral delivery systems for CRISPR. Viruses. 2019 Jan 4;11(1):28.
  37. Dong W, Kantor B. Lentiviral vectors for delivery of gene-editing systems based on CRISPR/Cas: current state and perspectives. Viruses. 2021 Jul 1;13(7):1288.
  38. Jiang C, Mei M, Li B, Zhu X, Zu W, Tian Y, Wang Q, Guo Y, Dong Y, Tan X. A non-viral CRISPR/Cas9 delivery system for therapeutically targeting HBV DNA and pcsk9 in vivo. Cell research. 2017 Mar;27(3):440-3.
  39. Kazemian P, Yu SY, Thomson SB, Birkenshaw A, Leavitt BR, Ross CJ. Lipid-nanoparticle-based delivery of CRISPR/Cas9 genome-editing components. Molecular pharmaceutics. 2022 May 20;19(6):1669-86.
  40. Ravichandran M, Maddalo D. Applications of CRISPR-Cas9 for advancing precision medicine in oncology: from target discovery to disease modeling. Frontiers in Genetics. 2023 Oct 16;14:1273994.
  41. Kaya M. The Role of CRISPR Technology in Advancing Personalized Medicine: Commercial and Ethical Considerations. Journal of Commercial Biotechnology. 2025;30(2):213-23.
  42. Yousefian M, Baharmast M. Artificial Intelligence-Assisted CRISPR Gene Editing: Current Advances, Clinical Challenges, and Future Directions in Precision Medicine. Avicenna Journal of Medical Biotechnology. 2026 Jan;18(1):3.

 

 

 

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