CRISPR-Cas9 in Human Health: A Scoping Review of Therapeutic Applications, Safety Challenges, and Ethical Frameworks
TL;DR
CRISPR-Cas9 has demonstrated considerable clinical potential across a range of therapeutic applications, particularly for selected monogenic disorders in which the strongest clinical evidence is currently available.
Abstract
Background: CRISPR-Cas9 has revolutionized genome editing by providing an efficient, versatile, and comparatively accessible platform for targeted genetic modification. Its rapid progression from laboratory innovation to clinical application has generated substantial interest across multiple therapeutic domains, while simultaneously raising significant safety, ethical, and regulatory concerns. Objective: This scoping review aimed to comprehensively map current evidence regarding the therapeutic applications, safety challenges, and ethical frameworks associated with CRISPR-Cas9 in human health. Methods: A scoping review methodology guided by the Arksey and O’Malley framework and PRISMA-ScR guidelines was employed. Comprehensive searches were conducted across PubMed, Dimensions, and Embase for peer-reviewed English-language studies published between 2015 and 2026. Eligible studies focused on CRISPR-Cas9 applications in human health, including therapeutic interventions, safety evaluations, ethical analyses, and regulatory considerations. A total of 32 studies met the inclusion criteria and underwent thematic synthesis. Results: CRISPR-Cas9 demonstrated substantial therapeutic promise across hematologic disorders, metabolic diseases, ophthalmologic conditions, oncology, immunotherapy, and rare genetic disorders. The most clinically advanced applications were observed in sickle cell disease, β-thalassemia, hereditary transthyretin amyloidosis, and hereditary angioedema, where clinical trials showed durable and potentially curative outcomes. However, major barriers remain, including off-target effects, genomic instability, delivery inefficiencies, immunogenicity, and limited long-term safety data. Ethical and regulatory concerns were prominent, particularly regarding germline editing, health equity, global governance, and accessibility. Conclusion: CRISPR-Cas9 has demonstrated considerable clinical potential across a range of therapeutic applications, particularly for selected monogenic disorders in which the strongest clinical evidence is currently available. Although important advances have been achieved, broader clinical implementation will require continued improvements in editing precision, long-term safety evaluation, delivery technologies, ethical oversight, equitable access, and harmonized regulatory frameworks.