A team of researchers led by Luigi Naldini at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) has developed a new strategy to significantly improve the precision and safety of CRISPR-Cas9 gene editing in human blood stem cells, potentially overcoming one of the major barriers limiting broader clinical application of genome editing therapies.
The study, published in Nature Biotechnology, introduces SMArT ("Selection by Means of Artificial Transactivators"), an innovative platform that achieves targeted integration of a gene-sized cassette and verifies the outcome of the procedure.
This strategy can be used to enrich edited hematopoietic stem and progenitor cells (HSPCs) to near purity while selectively removing cells carrying unintended and potentially harmful genomic alterations generated during editing.
The work was led by Luigi Naldini, director of SR-Tiget, and Samuele Ferrari, with Daniele Canarutto and Martina Fiumara as first authors.
CRISPR-Cas9 editing has transformed the field of genetic medicine by enabling targeted modification of disease-causing genes. The first CRISPR-based therapies—including exagamglogene autotemcel (Casgevy) for sickle cell disease and transfusion-dependent beta-thalassemia—have already received regulatory approval in multiple countries, marking a historic milestone for genome editing therapies. However, despite these advances, safety concerns remain.
