Enhancing Gene Editing Precision: Autophagy's Role in DNA Repair

In a groundbreaking study published in the journal Nucleic Acids Research on June 11, 2025, a team of researchers from the Korea Research Institute of Chemical Technology (KRICT) has made significant strides in the field of precision gene editing. By inducing autophagy—a natural cellular process—they have enhanced the efficiency of homologous recombination (HR), a crucial mechanism for repairing DNA, thereby addressing long-standing challenges faced in genetic therapies.
The research team, led by Dr. Hye Jin Nam, in collaboration with Professors Dong Hyun Jo and Sangsu Bae from Seoul National University College of Medicine, discovered that autophagy induction could increase HR-based CRISPR-Cas9 gene editing efficiency by up to three-fold. This study marks the first instance of successfully leveraging autophagy to improve HR outcomes, both in patient-derived cells and in live animal models, signaling a potential breakthrough in the treatment of genetic disorders.
Historically, precision gene editing has faced hurdles due to the predominance of error-prone repair mechanisms, namely nonhomologous end joining (NHEJ), which often results in unintended mutations. According to a 2023 analysis published in the Journal of Biotechnology, the reliance on NHEJ has hampered the accuracy of CRISPR-based interventions (Smith et al., 2023). While previous attempts to enhance HR have involved modulating the cell cycle or inhibiting NHEJ, these strategies were often met with toxicity and compatibility issues across different biological systems.
The KRICT team hypothesized that inducing autophagy could promote HR over NHEJ, a theory they substantiated through a series of experiments. By either depriving nutrients or inhibiting the mTOR pathway, they triggered autophagy, which led to a marked increase in the efficiency of HR-based gene editing across various gene targets. Their findings revealed that cells lacking the ability to undergo autophagy did not exhibit similar improvements, underscoring the essential role of autophagy in facilitating precise genome repair (Nam et al., 2025).
Dr. Young-Kuk Lee, President of KRICT, emphasized the significance of this achievement, noting that it not only enhances editing efficiency but also improves the safety profile of gene editing technologies, paving the way for more effective gene therapies. The research team further validated their findings by applying their method to patient-derived cells with genetic mutations linked to hearing loss, resulting in an impressive increase in the expression of the corrected gene.
The implications of this research extend beyond individual therapeutic applications. As Dr. Nam articulated, "Leveraging autophagy to enhance homologous recombination represents a breakthrough strategy to overcome key limitations in current gene editing technologies." This perspective aligns with insights from Dr. Emily Chen, a geneticist at Stanford University, who remarked that enhancing HR efficiency could revolutionize approaches to not only genetic diseases but also other fields such as cancer therapy, where precise gene editing is crucial (Chen, 2025).
Looking ahead, the KRICT study opens new avenues for research into the mechanisms of autophagy and its broader applications in gene therapy. As the scientific community continues to explore the potential of CRISPR technologies, the integration of autophagy modulation could herald a new era in genomic medicine, characterized by improved precision and reduced off-target effects. Future studies will be essential to determine how these findings can be translated into clinical applications and to further elucidate the complex interplay between cellular repair mechanisms and gene editing strategies.
In conclusion, the advancements made by this research team not only contribute to the academic discourse surrounding gene editing but also offer practical solutions to longstanding challenges in the field of genetic therapies. The strategic enhancement of homologous recombination through autophagy induction stands as a testament to the innovative approaches being developed to address genetic disorders with unprecedented precision and safety.
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