Revolutionizing Endodontics: Potential, Challenges and Ethical Concerns of CRISPR Technology in Endodontics

Authors

  • Isma Sajjad Sindh Institute of Oral Health Sciences, Jinnah Sindh Medical University, Karachi, Pakistan.
  • Mustafa Sajid Multan Medical and Dental College, Multan, Pakistan.
  • Syed Yawar Ali Abidi Sindh Institute of Oral Health Sciences, Jinnah Sindh Medical University, Karachi, Pakistan.
  • Maham Muneeb Lone Sindh Institute of Oral Health Sciences, Jinnah Sindh Medical University, Karachi, Pakistan.

DOI:

https://doi.org/10.36283/PJMD13-3/022

Keywords:

Endodontics, CRISPR, Genetics

Abstract

In the evolving landscape of endodontic therapy, our primary objective revolved around maintaining dental pulp vitality or intervening effectively when the pulp is irreparably damaged or infected. At the forefront of these groundbreaking advancements stands CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) gene-editing technology that has captivated the global scientific community. The origins of CRISPR hail from a natural defense mechanism employed by bacteria and archaea. These microorganisms capture snippets of DNA from invading viruses, creating a genomic library that serves as a historical record of past viral encounters. This remarkable natural process has paved the way for potentially transformative methods in treating a spectrum of dental pulp diseases and disorders. However, integrating CRISPR into clinical practice is not without its complexities and moral dilemmas. One of the foremost concerns is the reliability of the gene-editing process. To address this, there is a concerted effort within the scientific fraternity to refine the Cas9 enzyme further, to enhance the design of guide RNAs, and to develop sophisticated techniques for identifying and rectifying any inadvertent genetic modifications. In summary, the horizon of endodontic therapy is becoming increasingly promising, with CRISPR technology leading the charge. Hence, the objective of this review article was to provide a comprehensive overview of the potential, challenges, and ethical concerns of using CRISPR technology in the field of endodontics.

Keywords: Endodontics, CRISPR, Cas-9 Systems, Gene Editing, Genetic Engineering.

 

Author Biographies

  • Isma Sajjad, Sindh Institute of Oral Health Sciences, Jinnah Sindh Medical University, Karachi, Pakistan.

    Assistant Professor, Department of Operative Dentistry and Endodontics

  • Mustafa Sajid, Multan Medical and Dental College, Multan, Pakistan.

    Associate Professor

  • Syed Yawar Ali Abidi, Sindh Institute of Oral Health Sciences, Jinnah Sindh Medical University, Karachi, Pakistan.

    Dean, Faculty of Dentistry Professor & Head of Department, Operative Dentistry and Endodontics

  • Maham Muneeb Lone, Sindh Institute of Oral Health Sciences, Jinnah Sindh Medical University, Karachi, Pakistan.

    Assistant Professor, Department of Operative Dentistry and Endodontics

References

Chong RY, Goodis HE. Pulp biology and regeneration. In: Hargreaves’ and Cohen’s Pathways of the Pulp. 11th ed. Philadelphia: Elsevier; 2018. p. 28-51.

Torabinejad M, Walton RE. Endodontics: Principles and Practice. 5th ed. Philadelphia: Elsevier; 2014.

Otsu K, Kumakami-Sakano M, Fujiwara N, Kikuchi K, Keller L, Lesot H, et al. Stem cells for tooth regeneration: Current status and prospects. Front Physiol. 2014;5:36. doi: 10.3389/fphys.2014.00036.

Sinclair F, Begum AA, Dai CC, Toth I, Moyle PM. Recent advances in the delivery and applications of nonviral CRISPR/Cas9 gene editing. Drug Deliv Transl Res. 2023;13(5):1500-1519. doi: 10.1007/s13346-023-01320-z.

Jang YE, Kim Y, Kim SY, Kim BS. Predicting early endodontic treatment failure following primary root canal treatment. BMC Oral Health. 2024;24(1):327. doi: 10.1186/s12903-024-03974-8.

Mikkelsen NS, Bak RO. Enrichment strategies to enhance genome editing. J Biomed Sci. 2023;30:51. https://doi.org/10.1186/s12929-023-00943-1.

Introduction to the CRISPR/Cas9 system. Taraka Bio. 2024.

Wei X, Xu H, Zhou M, Zhou Q, Li M, Liu Y. Chemically modified microRNA delivery via DNA tetrahedral frameworks for dental pulp regeneration. J Nanobiotechnol. 2024; 22:150. https://doi.org/10.1186/s12951-024-02393-99.

Dubey AK, Gupta VK, Kujawska M, Orive G, Kim NY, Li C, et al. Exploring nano-enabled CRISPR-Cas-powered strategies for efficient diagnostics and treatment of infectious diseases. J Nanostruct Chem. 2022; 12:833-864. https://doi.org/10.1007/s40097-022-00472-7.

Jiang F, Doudna JA. CRISPR–Cas9 structures and mechanisms. Annu Rev Biophys. 2017;46:505-529. doi: 10.1146/annurev-biophys-062215-010822.

Chen X, Zhang Y, Wang Y, Chen J. The potential applications of CRISPR/Cas9-mediated genome editing in studying dental pulp biology and improving endodontic treatment. Stem Cell Res Ther. 2019;10(1):314.

Kwack KH, Lee HW. Clinical potential of dental pulp stem cells in pulp regeneration: current endodontic progress and future perspectives. Front Cell Dev Biol. 2022;10:857066. doi: 10.3389/fcell.2022.857066.

Mozaffari MS, Emami G, Khodadadi H, Baban B. Stem cells and tooth regeneration: prospects for personalized dentistry. EPMA J. 2019;10(1):31-42. doi: 10.1007/s13167-018-0156-4.

Bikard D, Marraffini LA. Innate and adaptive immunity in bacteria: Mechanisms of programmed genetic variation to fight bacteriophages. Curr Opin Immunol. 2012;24(1):15-20. doi: 10.1016/j.coi.2011.10.005.

Vendramini Y, Salles A, Portella FF, Brew MC, Steier L, de Figueiredo JA, et al. Antimicrobial effect of photodynamic therapy on intracanal biofilm: a systematic review of in vitro studies. Photodiagnosis Photodyn Ther. 2020; 32:102025. doi: 10.1016/j.pdpdt.2020.102025.

Yosef I, Manor M, Kiro R, Qimron U. Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria. Proc Natl Acad Sci U S A. 2015;112(23):7267-7272. doi: 10.1073/pnas.1500107112.

Wu Y, Battalapalli D, Hakeem MJ, Selamneni V, Zhang P, Draz MS, et al. Engineered CRISPR-Cas systems for the detection and control of antibiotic-resistant infections. J Nanobiotechnol. 2021; 19:401. https://doi.org/10.1186/s12951-021-01132-8.

Cai B, Chang S, Tian Y, Zhen S. CRISPR/Cas9 for hepatitis B virus infection treatment. Immun Inflamm Dis. 2023;11(5):e866. doi: 10.1002/iid3.866.

Schleidgen S, Dederer HG, Sgodda S, Cravcisin S, Lüneburg L, Cantz T, et al. Human germline editing in the era of CRISPR-Cas: risk and uncertainty, inter-generational responsibility, therapeutic legitimacy. BMC Med Ethics. 2020;21(1):87. https://doi.org/10.1186/s12910-020-00487-1.

Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR, O’Keeffe S, et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci. 2016;34(36):11929-11947. doi: 10.1523/JNEUROSCI.1860-14.2014

National Academies of Sciences, Engineering, and Medicine; National Academy of Medicine; National Academy of Sciences; Committee on Human Gene Editing: Scientific, Medical, and Ethical Considerations. Human Genome Editing: Science, Ethics, and Governance. Washington (DC): National Academies Press (US); 2017.

Lander ES, Baylis F, Zhang F, Charpentier E, Berg P, Bourgain C, et al. Adopt a moratorium on heritable genome editing. Nature. 2019;567(7747):165-168. doi: 10.1038/d41586-019-00726-5.

Gostimskaya I. CRISPR-Cas9: a history of its discovery and ethical considerations of its use in genome editing. Biochemistry (Mosc). 2022;87(8):777-788. doi: 10.1134/S0006297922080090.

Ayanoğlu FB, Elçin AE, Elçin YM. Bioethical issues in genome editing by CRISPR-Cas9 technology. Turk J Biol. 2020;44(2):110-120. doi: 10.3906/biy-1912-52.

Knoppers BM, Isasi R, Caulfield T, Kleiderman E, Bedford P, Illes J, et al. Human gene editing: revisiting Canadian policy. NPJ Regen Med. 2017;2:3. doi: 10.1038/s41536-017-0007-2

Svingen M, Jahren L. Making space for CRISPR: scientists’ translation work to make gene editing a legitimate technology. Sci Public Policy. 2024;51(1):15–27. https://doi.org/10.1093/scipol/scad050.

Sherkow JS, Dederer HG, Sgodda S, Cravcisin S, Lüneburg L, Cantz T, Heinemann T. Controlling CRISPR through law: legal regimes as precautionary principles. CRISPR J. 2019;2(5):325-33. doi: 10.1089/crispr.2019.0029

Rodriguez E. Ethical issues in genome editing using Crispr/Cas9 system. J Clin Res Bioeth. 2016;7:266. doi: 10.4172/2155-9627.1000266.

Jasanoff S, Hurlbut JB, Saha K. CRISPR democracy: gene editing and the need for inclusive deliberation. Issues Sci Technol. 2015;32(1):25-32.

Nature Editorial. License CRISPR patents for free to share gene editing globally. Nature. 2021;597(7874):7. doi: 10.1038/d41586-021-02420-x

Lima R, DelFiol FS, Balcão VM. Prospects for the use of new technologies to combat multidrug-resistant bacteria. Front Pharmacol. 2019;10:692. doi: 10.3389/fphar.2019.00692.

Kim J, Lee S, Cho SW. CRISPR/Cas9-mediated gene knockout in human dental pulp cells. J Dent Res. 2018;97(11):1255-62.

Muhammad I, Hassan M, Seung C. C5L2 CRISPR KO enhances dental pulp stem cell-mediated dentinogenesis via TrkB under TNFα-induced inflammation. Front Cell Develop Biol. 2024;12. doi: 10.3389/fcell.2024.1338419.

Rabaan AA, Al Fares MA, Almaghaslah M, Alpakistany T, Al Kaabi NA, Alshamrani SA, et al. Application of CRISPR-Cas system to mitigate superbug infections. Microorganisms. 2023;11(10):2404. doi: 10.3390/microorganisms11102404.

Takahashi K, Yamazaki K, Yamazaki M, Kato Y, Baba Y. Personalized medicine based on the pathogenesis and risk assessment of endodontic-periodontal lesions. J Pers Med. 2022;12(10):1688. doi: 10.3390/jpm12101688.

Lee M. Deep learning in CRISPR-Cas systems: a review of recent studies. Front Bioeng Biotechnol. 2023;11:1226182. doi: 10.3389/fbioe.2023.1226182.

Hosseinpour S, Gaudin A, Peters OA. A critical analysis of research methods and experimental models to study biocompatibility of endodontic materials. Int Endod J. 2022;55 (Suppl 2):346-369. doi: 10.1111/iej.13701.

Marimuthu A, Subramani RP, Deepika G. Gene therapy and CRISPR/Cas technology in Dentistry: a review. Dent J Adv Stud. 2024;12(1):49-54. doi: 10.5005/djas-11014-0033.

Ansori AN, Antonius Y, Susilo RJ, Hayaza S, Kharisma VD, Parikesit AA, et al. Application of CRISPR-Cas9 genome editing technology in various fields: A review. Narra J. 2023;3(2):e184. doi: 10.52225/narra.v3i2.184.

Krasilnikova O, Yakimova A, Ivanov S, Atiakshin D, Kostin AA, Sosin D, et al. Gene-activated materials in regenerative dentistry: Narrative review of technology and study results. Int J Mol Sci. 2023;24:16250. doi: https://doi.org/10.3390/ijms242216250.

Downloads

Published

2024-10-11

How to Cite

1.
Sajjad I, Sajid M, Abidi SYA, Lone MM. Revolutionizing Endodontics: Potential, Challenges and Ethical Concerns of CRISPR Technology in Endodontics. PJMD [Internet]. 2024 Oct. 11 [cited 2024 Oct. 12];13(3):160-6. Available from: https://ojs.zu.edu.pk/pjmd/article/view/2467

Similar Articles

You may also start an advanced similarity search for this article.