CRISPR-Cas Gene Editing in Rare Genetic Disorders: Breakthroughs, Risks, and the Road Ahead

CRISPR-Cas systems have revolutionized the therapeutic landscape for rare genetic disorders, offering unprecedented precision in correcting disease-causing mutations. This comprehensive review synthesizes recent breakthroughs in CRISPR-based therapies, including base editing and prime editing platforms that enable precise DNA modifications without double-strand breaks. We examine landmark clinical applications for disorders such as sickle cell disease, CPS1 deficiency, and transthyretin amyloidosis, highlighting efficacy data from ongoing trials. Significant risks including off-target effects, chromosomal rearrangements, immunogenicity, and unintended consequences of retrotransposition are critically evaluated alongside risk-mitigation strategies. The analysis extends to delivery challenges, ethical considerations of germline editing, and accessibility barriers. Emerging innovations in Cas enzyme engineering, tissue-specific delivery, and computational approaches are presented as promising solutions. With over 70 clinical trials currently underway and the first regulatory approvals secured, CRISPR therapies demonstrate transformative potential for monogenic disorders. However, long-term safety monitoring, equitable access, and ethical frameworks require concerted effort. This review concludes that strategic integration of technological advances with robust translational frameworks will accelerate the realization of durable CRISPR-based cures for the 300 million people affected by rare diseases worldwide.