CRISPR‐Cas9 and precision editing technologies linking functional genomics to clinical translation in genetic diseases
TL;DR
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
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.