CRISPR-Cas9 and precision editing technologies linking functional genomics to clinical translation in genetic diseases

Abstract

Background CRISPR-Cas9 and derivative precision-editing platforms increasingly connect pathogenic variant interpretation with functional genomics and therapeutic development in genetic diseases. This narrative review focuses on a variant-mechanism-driven framework for matching editing strategies to mutation structure, functional consequence, disease-model evidence, delivery feasibility, safety risk, and translational readiness. Main body The review summarizes how monogenic, polygenic, coding, non-coding, mitochondrial, and complex disease contexts influence the choice of canonical Cas9 editing, base editing, prime editing, Cas variants, CRISPR interference/activation, epigenome editing, and disease-model systems. It further compares ex vivo and in vivo delivery routes, safety assessment strategies, immunogenicity and genotoxicity concerns, and clinical implementation barriers, including CMC/manufacturing scalability, long-term follow-up, affordability, and regulatory oversight. Current evidence supports the clinical maturity of ex vivo hematopoietic editing, whereas most in vivo and precision-repair approaches remain constrained by delivery, durability, product heterogeneity, and safety uncertainties. Conclusion The central conclusion is that future CRISPR-based interventions should be judged not only by editability, but by whether molecular correction can be translated into durable, safe, manufacturable, and clinically meaningful benefit.

Abstract of "CRISPR-Cas9 and precision editing technologies linking functional genomics to clinical translation in genetic diseases" by Wen Z, Su J, https://doi.org/10.1002/ctm2.70764, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.