Innovative Approach to In Vivo Blood Stem Cell Gene Therapy Discovered

A groundbreaking study conducted by researchers at the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan has revealed a promising new strategy for treating blood disorders through direct gene therapy in newborns. The team has identified a critical window shortly after birth when circulating blood stem cells are most accessible for genetic modification via systemic delivery of lentiviral vectors. This approach could eliminate the need for invasive procedures like stem cell extraction and chemotherapy used in traditional ex vivo gene therapy.

Published in the journal Nature, the research demonstrates that in newborn mice—and potentially humans—the number of hematopoietic stem and progenitor cells in the bloodstream is substantially higher in the early postnatal period. During this window, intravenous injection of lentiviral vectors successfully achieved long-term engraftment and multilineage blood cell production, showing therapeutic benefits in mouse models of severe immunodeficiency (ADA-SCID), bone disease (autosomal recessive osteopetrosis), and bone marrow failure syndrome (Fanconi anemia). Notably, in the Fanconi anemia model, corrected stem cells gradually repopulated the blood system and prevented marrow failure.

To extend the treatment window, the researchers used approved mobilizing drugs like G-CSF and Plerixafor, which increased stem cell circulation and improved gene transfer efficiency in older mice. Encouragingly, human studies indicated that newborns also have detectable circulating hematopoietic stem cells, suggesting this method could be feasible in clinical settings.

While current ex vivo gene therapies are highly effective, they are resource-intensive and invasive. This in vivo approach offers a less invasive alternative that could be especially beneficial for early treatment of genetic blood diseases in infants. Future research aims to understand why early-age stem cells are more receptive to gene transfer and how to replicate this permissiveness at later ages, potentially broadening the applicability of in vivo gene therapy for lifelong benefits.

In summary, this innovative technique highlights the potential for in vivo genetic modification of blood stem cells during a natural postnatal window, paving the way for alternative treatments for severe blood disorders, with promising implications for human patients.