Future development directions lie in integrating artificial intelligence to optimize editing design, perfecting lifelong safety monitoring systems, constructing ethical consensus across multicultural backgrounds, promoting deep synergy between technological innovation and humanistic care, and ultimately achieving a paradigm shift in genetic disease treatment from symptom management to etiological eradication.
Abstract
Gene editing technology is fundamentally reshaping the paradigm of genetic disease treatment, and its clinical translation marks the entry of modern medicine into an era of precise intervention. The CRISPR-Cas9 system, with its programmable targeting capability, provides radical solutions for monogenic genetic diseases, achieving historic breakthroughs in the treatment of thalassemia and sickle cell disease. Technological iterations have spawned new paradigms of base editing and prime editing, enabling single-base precise correction while circumventing double-strand break risks, representing a qualitative leap in the safety dimension. Ethical controversies focus on the unpredictability of off-target effects, the intergenerational responsibility boundaries of germline editing, and the social equity of technology benefit distribution, urgently requiring the establishment of global collaborative governance mechanisms. Innovations in delivery systems have broken through organ-targeting bottlenecks, making in vivo in situ editing possible. Future development directions lie in integrating artificial intelligence to optimize editing design, perfecting lifelong safety monitoring systems, constructing ethical consensus across multicultural backgrounds, promoting deep synergy between technological innovation and humanistic care, and ultimately achieving a paradigm shift in genetic disease treatment from symptom management to etiological eradication.
This review systematically summarizes the developmental logic, core mechanisms, clinical applications, advantages and limitations of the three generations of CRISPR-Cas technology in monogenic disorders, and analyzes the key challenges such as delivery efficiency, long-term safety, and treatment accessibility.
Yiwen Wang· Theoretical and Natural Scie...· 0 citations
CRISPR-Cas systems, base editing, and prime editing have made precise genetic interventions possible, and several approved therapies now treat monogenic disorders that were previously untreatable. Heritable genome editing remains ethically contested. We argue that heritable interventions should not be treated as a single category subject to uniform prohibition. We distinguish three targets: catastrophic monogenic disorders, polygenic risk reduction, and non-disease trait enhancement. For catastrophic monogenic conditions in which preimplantation selection cannot yield unaffected embryos, heritable editing is permissible, and the duty of beneficence toward future persons may require it. When the alternative is certain severe suffering or early death, the expected benefits clearly outweigh the risks. For polygenic interventions, current scientific uncertainty makes clinical application premature: predictive validity remains insufficient and pleiotropic effects are poorly understood. For enhancement, the case is weaker still. Some of its benefits are positional; the risks of social stratification are significant; and the evidence base is absent. We conclude that governance frameworks should permit what the evidence supports under stringent safeguards and prohibit what it does not. The central ethical questions concern welfare, not appeals to nature or abstract notions of dignity. Where the evidence warrants it, failing to pursue heritable gene therapy responsibly may itself be an ethical failure. We outline a translational pathway for ethical germline gene editing.
Julian Savulescu, Sebastian Porsdam Mann, C. Gyngell et al.· i Medicina· 0 citations
The potential application of CRISPR technology for the possible management of geneticbased conditions, including sickle-cell anemia, β-thalassemia, cystic fibrosis, and Duchenne muscular dystrophy is described.
M. Veer, Poonam Nikam, Omkar More et al.· International Journal of Dru...· 0 citations
CRISPR has progressed from an experimental genome-engineering technology to a clinically relevant therapeutic platform, although its future impact will depend on the ability to combine molecular precision and durable therapeutic benefit with rigorous safety assessment, responsible governance, and equitable access across diverse populations and healthcare systems.
G. Alejandro, Ortega Moreno, G. Amaya et al.· International science journa...· 0 citations
The success of CRISPR-Cas9 in monogenic diseases represents the prelude to precision medicine, whereas conquering complex diseases will require systematic leaps in target discovery, delivery technology, and safety profiles.
This article synthesizes contemporary advancements in CRISPR-mediated mammalian genome modification, detailing core mechanisms – such as guide RNA and the Cas9 endonuclease – alongside next-generation modalities, including base and prime editing.
Olga Aldoshina, Dmitriy Lazarev, E. Smirnova· Veterinariya, Zootekhniya i...· 0 citations