Safer gene editing: new prospects for treating inherited diseases

A study published in the international scientific journal Molecular Therapy, with Professor Raffaella Di Micco as senior author, identifies a promising strategy to protect stem cells during gene-editing procedures. Professor Di Micco is Professor of General Pathology at the Scuola Universitaria Superiore IUSS Pavia and leads a research group at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) at IRCCS Ospedale San Raffaele in Milan.

Gene editing of blood stem cells could open up new therapeutic opportunities for inherited diseases. However, the process can expose cells to stress and potentially cause DNA damage.

A new study, with Professor Raffaella Di Micco as senior author, Professor of General Pathology at the Scuola Universitaria Superiore IUSS Pavia and research group leader at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) at IRCCS Ospedale San Raffaele in Milan, has identified a potential strategy to overcome these limitations.

The researchers demonstrated that temporarily inhibiting p38 MAPK, a protein involved in the cellular stress response, improves the quality of genetically modified blood stem cells and their ability to maintain long-term functionality.

This effect was also observed in cells undergoing editing of clinically relevant genes associated with immune system disorders.

Importantly, comprehensive analyses found no evidence of an increase in harmful genetic alterations following p38 inhibition. On the contrary, treated cells showed fewer signs of DNA damage and fewer mutations after transplantation and long-term follow-up.

These findings suggest that temporary p38 inhibition could represent a promising strategy for making gene-editing approaches safer and more effective, paving the way for future therapeutic applications.

The study was published in the scientific journal Molecular Therapy.

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