Research progress of gene correction for genetic diseases via in vivo prime editing

Curative therapies for genetic diseases caused by pathogenic mutations demand precise and safe genome editing technologies. Prime editing (PE), a CRISPR-Cas9-derived technology that enables precise base conversions without double-strand breaks (DSBs), has emerged as a transformative tool with the ability to correct 89% of human pathogenic mutations. However, transitioning PE from preclinical models to clinical applications faces critical challenges, particularly in the development of in vivo delivery systems and scalable manufacturing. This review systematically summarizes advances of in vivo PE therapeutics, focusing on the therapeutic outcomes across some retinal, metabolic, and hematologic genetic diseases. We further dissect barriers to clinical translation, including in the immunogenicity of viral vectors, off-target risks in nondividing cells, and large-scale production bottlenecks. By highlighting the unique advantages of in vivo PE and proposing actionable solutions for scalable manufacturing, the work provides a roadmap for accelerating in vivo PE-based therapies toward clinical reality.