A new approach to gene therapy may revolutionize how inherited blood diseases like sickle cell disease and Fanconi anemia are treated—by editing blood stem cells directly inside the body. Researchers from the IRCCS San Raffaele Scientific Institute in Italy have successfully edited genes in infant mice using a single injection, bypassing the need to extract, modify, and reintroduce stem cells—a process that is currently complex, costly, and physically demanding for patients.

The new treatment leverages a critical time window shortly after birth, when blood stem cells naturally circulate from the liver to the bone marrow. During this phase, stem cells are more accessible in the bloodstream, making them an ideal target for in vivo gene editing. In adult patients, these cells are typically hidden deep in the bone marrow, making them harder to reach.

In the study, the team delivered gene-editing instructions via a modified virus called LV, which safely ferries genetic material into the body. This method successfully targeted and reprogrammed circulating stem cells in newborn mice. The edits remained stable over time and were even retained when transplanted into other mice. When tested in young adult mice, the effect was enhanced using chemical agents that encouraged more blood stem cells to circulate.

Importantly, the treatment showed long-lasting effects across multiple age groups, with the strongest results in newborns. In one test, the therapy corrected a severe bone disorder called autosomal recessive osteopetrosis (ARO), allowing treated mice to build bones normally and survive significantly longer than untreated peers.

The approach also showed promise against other genetic conditions. Mice with an immune-compromising metabolic disorder survived beyond weaning after treatment, displaying normal health. The most notable results came from experiments on Fanconi anemia—a challenging disorder caused by faulty DNA repair mechanisms. This disease is notoriously difficult to treat with traditional methods due to the low number of usable stem cells. Yet, with a single injection in newborn mice, the team restored normal immune cell production for over a year.

The timing of treatment appears to be critical. As mice age, the number of circulating blood stem cells drops significantly. However, the researchers demonstrated that approved “mobilizer” drugs can reopen this therapeutic window by encouraging stem cells to circulate again, potentially expanding the age range for treatment.

Human infants also have high levels of circulating blood stem cells after birth, suggesting this method could one day apply to people. Although editing stem cells outside the body remains more efficient for now, the study offers a promising pathway toward simpler, more accessible gene therapy—particularly for patients who lack enough stem cells for traditional treatment.

The technology may not yet match the efficiency of current ex vivo methods, but for conditions like Fanconi anemia and severe immunodeficiencies, where early treatment is crucial and stem cell supply is limited, this approach could offer a life-saving alternative. Further research is underway to translate these findings into human clinical trials.

By Impact Lab