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Ethical Challenges of Gene Editing in Biomedical Research and Healthcare: Patient Autonomy, Safety, Equity and Governance
Subject area: Biological & Medical Sciences · Area of research: Bioethics, Genome Editing and Biomedical Ethics
Abstract
Gene editing is a reality in clinical practice. Since late 2023 we have seen the approval of an ex vivo CRISPR-Cas9 therapy for sickle cell disease and transfusion dependent beta thalassaemia and in July 2026 the US expanded the label to include children as young as two years of age; also in 2025 a personalized in vivo base editing therapy was made available to an infant; heritable editing is still off the table in most which have a policy against it. We look at four ethical issues which arise from this consent and autonomy, safety, equity and governance which we separate out into categories of somatic, personal and heritable editing and research as opposed to care. We also report that (1) which informed consents were given in past gene transfer studies was in fact to present a greater benefit than what was achieved and in exa-cel we note that the primary serious issues including that of infertility and a fatal liver issue in a child came from the treatment regimen which at the time was under chemotherapeutic conditioning, hence consents had to cover the full treatment process; (2) while regulators at the time found the benefit risk ratio for ex vivo to be favorable they did so based on a 15 year follow up which in in vivo editing we see to have caused a serious liver issue also which in human embryo studies we see to also present a case of chromosome loss which in turn supports the case for licensed somatic use and the to continue to put on hold heritable use; (3) what we do see is that access is the issue not efficacy, we had 64 infusions world wide in 2025 which is against a background of tens of thousands that are eligible and also that the majority of people with SCD live in sub-Saharan Africa; and (4) governance is firm on heritable editing and uneven elsewhere, with public engagement recommended more often than connected to decisions. The literature is concentrated on SCD and exa-cel, and we identify priority evidence gaps.
Keywords
CRISPR; equity; gene editing; governance; informed consent
References
[1] Frangoul H, et al. Exagamglogene autotemcel for severe sickle cell disease. The New England Journal of Medicine. 2024;390(18):1649–1662. https://doi.org/10.1056/NEJMoa2309676
[2] U.S. Food and Drug Administration. FDA approves first gene therapies to treat patients with sickle cell disease. Press release, Dec. 8, 2023. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease
[3] Parums DV. Editorial: First regulatory approvals for CRISPR-Cas9 therapeutic gene editing for sickle cell disease and transfusion-dependent β-thalassemia. Medical Science Monitor. 2024;30:e944204. https://doi.org/10.12659/MSM.944204
[4] European Medicines Agency. Casgevy: EPAR. Medicine overview and public assessment summary, 2024. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/casgevy
[5] U.S. Food and Drug Administration. FDA approves first gene therapy for young children with sickle cell disease. Press release, Jul. 1, 2026. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-young-children-sickle-cell-disease
[6] Musunuru K, et al. Patient-specific in vivo gene editing to treat a rare genetic disease. The New England Journal of Medicine. 2025;392(22):2235–2243. https://doi.org/10.1056/NEJMoa2504747
[7] Gori JL, et al. Prime editing for p47phox-deficient chronic granulomatous disease. The New England Journal of Medicine. 2026;394(12):1195–1203. https://doi.org/10.1056/NEJMoa2509807
[8] Chen Q, Ma Y, Labude M, Schaefer GO, Xafis V, Mills P. Making sense of it all: Ethical reflections on the conditions surrounding the first genome-edited babies (Version 2). Wellcome Open Research. 2020;5:216. https://doi.org/10.12688/wellcomeopenres.16295.2
[9] Li J, Walker S, Nie J, Zhang X. Experiments that led to the first gene-edited babies: The ethical failings and the urgent need for better governance. Journal of Zhejiang University-SCIENCE B. 2019;20(1):32–38. https://doi.org/10.1631/jzus.B1800624
[10] Organising Committee of the Third International Summit on Human Genome Editing. Statement from the Organising Committee of the Third International Summit on Human Genome Editing. The Royal Society, Mar. 8, 2023. Available from: https://royalsociety.org/news/2023/03/statement-third-international-summit-human-genome-editing/
[11] Perillat L, McFadyen A, Furlong P, Anderson J. A conceptual model and practical guidance for the development, administration, and evaluation of individualized therapies. Frontiers in Medicine. 2025;12:1493832. https://doi.org/10.3389/fmed.2025.1493832
[12] Pougnet R, Derbez B, Troadec MB. Mapping the ‘ethical’ controversy of human heritable genome editing: A multidisciplinary approach. Asian Bioethics Review. 2023;15(2):189–204. https://doi.org/10.1007/s41649-022-00234-1
[13] van Hooff LC, Merz EM, Kidane Gebremeskel AS, de Jong JA, Burchell GL, Lunshof JE. Balancing benefits and burdens: A systematic review on ethical and social dimensions of gene and cell therapies for hereditary blood diseases. BMC Medical Ethics. 2025;26:36. https://doi.org/10.1186/s12910-025-01188-3
[14] Wiley L, et al. The ethics of human embryo editing via CRISPR-Cas9 technology: A systematic review of ethical arguments, reasons, and concerns. HEC Forum. 2025;37(2):267–303. https://doi.org/10.1007/s10730-024-09538-1
[15] Zarghamian P, Klermund J, Cathomen T. Clinical genome editing to treat sickle cell disease—A brief update. Frontiers in Medicine. 2023;9:1065377. https://doi.org/10.3389/fmed.2022.1065377
[16] Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature. 2016;533(7603):420–424. https://doi.org/10.1038/nature17946
[17] Anzalone AV, et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 2019;576(7785):149–157. https://doi.org/10.1038/s41586-019-1711-4
[18] Martin L, et al. In vivo delivery strategies for therapeutic CRISPR genome editing. International Journal of Biological Sciences. 2026;22(12):6539–6581. https://doi.org/10.7150/ijbs.133162
[19] Kalter N, et al. Off-target effects in CRISPR-Cas genome editing for human therapeutics: Progress and challenges. Molecular Therapy: Nucleic Acids. 2025;36(3):102636. https://doi.org/10.1016/j.omtn.2025.102636
[20] Intellia Therapeutics, Inc. Intellia Therapeutics announces third quarter 2025 financial results and recent updates. Press release, Nov. 6, 2025. Available from: https://ir.intelliatx.com/node/12311/pdf
[21] Frangoul H, et al. Exa-cel in children with transfusion-dependent β-thalassemia or sickle cell disease. The New England Journal of Medicine. 2026;395(10):947–958. https://doi.org/10.1056/NEJMoa2603387
[22] U.S. Food and Drug Administration. Human gene therapy products incorporating human genome editing: Guidance for industry. Center for Biologics Evaluation and Research, 2024. Available from: https://www.fda.gov/media/156894/download
[23] Alanis-Lobato G, et al. Frequent loss of heterozygosity in CRISPR-Cas9–edited early human embryos. Proceedings of the National Academy of Sciences. 2021;118(22):e2004832117. https://doi.org/10.1073/pnas.2004832117
[24] Zuccaro MV, et al. Allele-specific chromosome removal after Cas9 cleavage in human embryos. Cell. 2020;183(6):1650–1664.e15. https://doi.org/10.1016/j.cell.2020.10.025
[25] U.S. Food and Drug Administration. Considerations for the use of the plausible mechanism framework to develop individualized therapies that target specific genetic conditions with known biological cause: Draft guidance for industry. Docket No. FDA-2026-D-1256, 2026. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-use-plausible-mechanism-framework-develop-individualized-therapies-target-specific
[26] Baylis F, Darnovsky M, Hasson K, Krahn TM. Human germline and heritable genome editing: The global policy landscape. The CRISPR Journal. 2020;3(5):365–377. https://doi.org/10.1089/crispr.2020.0082
[27] Evans JH. Setting ethical limits on human gene editing after the fall of the somatic/germline barrier. Proceedings of the National Academy of Sciences. 2021;118(22):e2004837117. https://doi.org/10.1073/pnas.2004837117
[28] Almeida M, Ranisch R. Beyond safety: Mapping the ethical debate on heritable genome editing interventions. Humanities and Social Sciences Communications. 2022;9:139. https://doi.org/10.1057/s41599-022-01147-y
[29] Ranisch R, Trettenbach K, Árnason GÁ. Initial heritable genome editing: Mapping a responsible pathway from basic research to the clinic. Medicine. 2023;26:21–35. https://doi.org/10.1007/s11019-022-10115-x
[30] Lau PL. Addressing cognitive vulnerabilities through genome and epigenome editing: Techno-legal adaptations for persons with intellectual disabilities. European Journal of Health Law. 2022;29:409–434. https://doi.org/10.1163/15718093-bja10085
[31] Arnold SJAN, Houtman D, Retel Helmrich IRA, Hilberink SR, Riedijk SR. An exploration of the perspectives of Dutch adults experiencing a genetic condition on human germline gene editing. Journal of Community Genetics. 2025;16(5):489–501. https://doi.org/10.1007/s12687-025-00792-5
[32] Ramos PD, Almeida MS, Olsson IAS. What do people think about genetic engineering? A systematic review of questionnaire surveys before and after the introduction of CRISPR. Frontiers in Genome Editing. 2023;5:1284547. https://doi.org/10.3389/fgeed.2023.1284547
[33] Sawai T, Hatta T, Akatsuka K, Fujita M. Human genome editing in clinical applications: Japanese lay and expert attitudes. Frontiers in Genetics. 2023;14:1205092. https://doi.org/10.3389/fgene.2023.1205092
[34] Persaud A, Desine S, Blizinsky K, Bonham VL. A CRISPR focus on attitudes and beliefs toward somatic genome editing from stakeholders within the sickle cell disease community. Genetics in Medicine. 2019;21(8):1726–1734. https://doi.org/10.1038/s41436-018-0409-6
[35] Desine S, Hollister BM, Abdallah KE, Persaud A, Hull SC, Bonham VL. The meaning of informed consent: Genome editing clinical trials for sickle cell disease. AJOB Empirical Bioethics. 2020;11(4):195–207. https://doi.org/10.1080/23294515.2020.1818876
[36] Sharma A, et al. Gene therapy in sickle cell disease: Attitudes and informational needs of patients and caregivers. Pediatric Blood & Cancer. 2023;70(6):e30319. https://doi.org/10.1002/pbc.30319
[37] Sinha CB, Bakshi N, Ross D, Loewenstein G, Krishnamurti L. Primary caregiver decision-making in hematopoietic cell transplantation and gene therapy for sickle cell disease. Pediatric Blood & Cancer. 2021;68:e28749. https://doi.org/10.1002/pbc.28749
[38] Kimmelman J, Palmour N. Therapeutic optimism in the consent forms of phase 1 gene transfer trials: An empirical analysis. Journal of Medical Ethics. 2005;31(4):209–214. https://doi.org/10.1136/jme.2003.006247
[39] Henderson GE, et al. Uncertain benefit: Investigators’ views and communications in early phase gene transfer trials. Molecular Therapy. 2004;10(2):225–231. https://doi.org/10.1016/j.ymthe.2004.05.013
[40] O’Hara SE, Halpern J. How voluntary consent may be overlooked in gene editing clinical trials. Medical Research Archives. 2024;12(1). https://doi.org/10.18103/mra.v12i1.5046
[41] Munung NS, et al. Looking ahead: Ethical and social challenges of somatic gene therapy for sickle cell disease in Africa. Gene Therapy. 2024;31:202–208. https://doi.org/10.1038/s41434-023-00429-7
[42] Dalal V, Jotwani G, Yadav ML. Redefining informed consent form in cell and gene therapy trials. Perspectives in Clinical Research. 2024;15:4–9. https://doi.org/10.4103/picr.picr_244_22
[43] Nickel RS, Maher JY, Hsieh MH, Davis MF, Hsieh MM, Pecker LH. Fertility after curative therapy for sickle cell disease: A comprehensive review to guide care. Journal of Clinical Medicine. 2022;11(9):2318. https://doi.org/10.3390/jcm11092318
[44] Lee TL, Sawai T. Navigating equity in global access to genome therapy: Expanding access to potentially transformative therapies and benefiting those in need requires global policy changes. Frontiers in Genetics. 2024;15:1381172. https://doi.org/10.3389/fgene.2024.1381172
[45] Thaldar D, et al. A deliberative public engagement study on heritable human genome editing among South Africans: Study results. PLOS ONE. 2022;17(11):e0275372. https://doi.org/10.1371/journal.pone.0275372
[46] Borham A, Elgarhy FM, Moghith A, Elswefy MT, Mansour RI, Bakr M. Navigating the human gene editing scene and proposing a new governance framework in Africa: From knowledge to policy to action. Frontiers in Genome Editing. 2026;8:1866004. https://doi.org/10.3389/fgeed.2026.1866004
[47] Toofan P, Singh M, Brooks A, McLuckie K. Non-clinical safety considerations on genome editing using the CRISPR/Cas system. Genes & Diseases. 2025. https://doi.org/10.1016/j.gendis.2025.101785
[48] Bao C, et al. Chronic in vivo CRISPR-Cas genome editing: Challenges, long-term safety, and outlook. Cells. 2026;15(2):156. https://doi.org/10.3390/cells15020156
[49] U.S. Food and Drug Administration. Safety assessment of genome editing in human gene therapy products using next-generation sequencing: Draft guidance for industry. 2026. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/safety-assessment-genome-editing-human-gene-therapy-products-using-next-generation-sequencing
[50] Beaney A. FDA releases hold on second of Intellia’s ATTR-CM gene therapy trials. Clinical Trials Arena, Mar. 3, 2026. Available from: https://www.clinicaltrialsarena.com/newsletters/fda-releases-hold-on-second-of-intellias-attr-cm-gene-therapy-trials
[51] Rueda J, de Miguel Beriain Í, Montoliu L. Affordable pricing of CRISPR treatments is a pressing ethical imperative. The CRISPR Journal. 2024;7(5):220–226. https://doi.org/10.1089/crispr.2024.0042
[52] Thomson AM, et al. Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000–2021: A systematic analysis from the Global Burden of Disease Study 2021. The Lancet Haematology. 2023;10(8):e585–e599. https://doi.org/10.1016/S2352-3026(23)00118-7
[53] CRISPR Therapeutics AG. CRISPR Therapeutics provides business update and reports fourth quarter and full year 2025 financial results. Form 8-K, Exhibit 99.1, U.S. Securities and Exchange Commission, 2026. Available from: https://www.sec.gov/Archives/edgar/data/1674416/000119312526048873/crsp-ex99_1.htm
[54] CRISPR Therapeutics AG. CRISPR Therapeutics provides business update and reports third quarter 2025 financial results. Press release, Nov. 2025. Available from: https://ir.crisprtx.com/news-releases/news-release-details/crispr-therapeutics-provides-business-update-and-reports-third-6
[55] Centers for Medicare & Medicaid Services. CMS expands access to lifesaving gene therapies through innovative state agreements. Press release, Jul. 15, 2025. Available from: https://www.cms.gov/newsroom/press-releases/cms-expands-access-lifesaving-gene-therapies-through-innovative-state-agreements
[56] Green RC, Lautenbach D, McGuire AL. GINA, genetic discrimination, and genomic medicine. The New England Journal of Medicine. 2015;372(5):397–399. https://doi.org/10.1056/NEJMp1404776
[57] Parliamentary Assembly of the Council of Europe. Recommendation 2264 (2023): Heritable genome editing in human beings. 2023. Available from: https://pace.coe.int/en/files/33182/pdf
[58] Soni S. Recent developments in the regulation of heritable human genome editing. Journal of Bioethical Inquiry. 2024;21:15–18. https://doi.org/10.1007/s11673-023-10332-w
[59] WHO Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing. Human genome editing: A framework for governance. World Health Organization, Geneva, Switzerland, 2021. Available from: https://www.who.int/publications/i/item/9789240030060
[60] WHO Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing. Human genome editing: Recommendations. World Health Organization, Geneva, Switzerland, 2021. Available from: https://www.who.int/publications/i/item/9789240030381
[61] Marchant GE. Global governance of human genome editing: What are the rules? Annual Review of Genomics and Human Genetics. 2021;22:385–405. https://doi.org/10.1146/annurev-genom-111320-091930
[62] Shozi B, Kamwendo T, Kinderlerer J, Thaldar DW, Townsend B, Botes M. Future of global regulation of human genome editing: A South African perspective on the WHO draft governance framework on human genome editing. Journal of Medical Ethics. 2022;48:165–168. https://doi.org/10.1136/medethics-2020-106863
[63] Conley JM, et al. The promise and reality of public engagement in the governance of human genome editing research. The American Journal of Bioethics. 2023;23(7):9–16. https://doi.org/10.1080/15265161.2023.2207502
[64] Barlevy D, et al. Governing with public engagement: An anticipatory approach to human genome editing. Science and Public Policy. 2024;51(4):680–691. https://doi.org/10.1093/scipol/scae010
[65] Dryzek JS, et al. Global citizen deliberation on genome editing. Science. 2020;369(6510):1435–1437. https://doi.org/10.1126/science.abb5931
How to cite this paper
@article{1724610,
author = {Hassan Bashir Mukhtar, Musab Muhammad Bello},
title = {Ethical Challenges of Gene Editing in Biomedical Research and Healthcare: Patient Autonomy, Safety, Equity and Governance},
journal = {Iconic Research And Engineering Journals},
year = {2026},
volume = {10},
number = {5},
pages = {415-428},
issn = {2456-8880},
url = {https://www.irejournals.com/formatedpaper/1724610.pdf},
abstract = {Gene editing is a reality in clinical practice. Since late 2023 we have seen the approval of an ex vivo CRISPR-Cas9 therapy for sickle cell disease and transfusion dependent beta thalassaemia and in July 2026 the US expanded the label to include children as young as two years of age; also in 2025 a personalized in vivo base editing therapy was made available to an infant; heritable editing is still off the table in most which have a policy against it. We look at four ethical issues which arise from this consent and autonomy, safety, equity and governance which we separate out into categories of somatic, personal and heritable editing and research as opposed to care. We also report that (1) which informed consents were given in past gene transfer studies was in fact to present a greater benefit than what was achieved and in exa-cel we note that the primary serious issues including that of infertility and a fatal liver issue in a child came from the treatment regimen which at the time was under chemotherapeutic conditioning, hence consents had to cover the full treatment process; (2) while regulators at the time found the benefit risk ratio for ex vivo to be favorable they did so based on a 15 year follow up which in in vivo editing we see to have caused a serious liver issue also which in human embryo studies we see to also present a case of chromosome loss which in turn supports the case for licensed somatic use and the to continue to put on hold heritable use; (3) what we do see is that access is the issue not efficacy, we had 64 infusions world wide in 2025 which is against a background of tens of thousands that are eligible and also that the majority of people with SCD live in sub-Saharan Africa; and (4) governance is firm on heritable editing and uneven elsewhere, with public engagement recommended more often than connected to decisions. The literature is concentrated on SCD and exa-cel, and we identify priority evidence gaps.},
keywords = {CRISPR; equity; gene editing; governance; informed consent},
month = {November},
}