Prime Editing Moves Toward In Vivo Gene Correction for Genetic Diseases

Curative treatments for genetic diseases caused by pathogenic mutations require genome editing tools that are both precise and safe. A review published in Molecular Genetics and Genomics examines prime editing, a CRISPR-Cas9-derived technology that enables precise base conversions without creating double-strand breaks in DNA. According to the review, prime editing has emerged as a transformative tool with the ability to correct 89 percent of human pathogenic mutations.

The review focuses specifically on in vivo prime editing therapeutics, summarizing advances and therapeutic outcomes across retinal, metabolic, and hematologic genetic diseases. It systematically summarizes advances of in vivo prime editing therapeutics, with particular attention to therapeutic outcomes across retinal, metabolic, and hematologic genetic diseases.

Despite that promise, the authors identify a set of barriers that currently separate preclinical success from clinical reality. The first is delivery. Getting the prime editing machinery into the right cells inside a living patient remains a central engineering problem. The review identifies the immunogenicity of viral vectors as a barrier to clinical translation. The review also flags off-target risks in nondividing cells as a barrier to clinical translation.

Scalable manufacturing forms another major barrier. The review identifies large-scale production bottlenecks as a further barrier to clinical translation. The review proposes actionable solutions for scalable manufacturing.

The review highlights the unique advantages of in vivo prime editing and proposes actionable solutions for scalable manufacturing, providing a roadmap for accelerating in vivo PE-based therapies toward clinical reality. The review summarizes advances of in vivo prime editing therapeutics, focusing on therapeutic outcomes across retinal, metabolic, and hematologic genetic diseases, and dissects barriers to clinical translation. The work consolidates those findings and identifies where the field must focus to move in vivo prime editing-based therapies toward clinical reality.

By highlighting the unique advantages of in vivo prime editing and pairing them with concrete proposals for delivery, safety, and manufacturing, the review offers a structured agenda for the next phase of the field. The review's central message is that accelerating in vivo prime editing-based therapies toward clinical reality requires addressing delivery systems, immunogenicity, off-target risks, and scalable manufacturing.

Subject of Research: In vivo prime editing as a gene-correction strategy for genetic diseases

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

Article References: Shuran, Z., Yuzhen, H., Zili, Z., Wenming, H., Baosheng, Z., & Ying, C. (2026). Research progress of gene correction for genetic diseases via in vivo prime editing. Molecular Genetics and Genomics, 301(1), Article 210. https://doi.org/10.1007/s00438-026-02535-8

Image Credits: AI Generated

DOI: 10.1007/s00438-026-02535-8

Keywords: prime editing, CRISPR-Cas9, gene therapy, genetic diseases, in vivo delivery, viral vectors, retinal disease, metabolic disease, hematologic disease, off-target effects, immunogenicity, manufacturing