Systemic delivery of phagocytosis-shielded retroviral vectors enables in vivo HSC gene therapy for sickle cell disease.

Phagocytosis-shielded BaEVRLess-pseudotyped vectors achieve up to 8.8% gene marking in human HSCs in vivo, enabling potential gene therapy for sickle cell disease.

• Why it matters: Current ex vivo HSC gene therapy for SCD involves complex procedures, limiting accessibility; in vivo delivery could simplify treatment and broaden patient access.
• What they did: Researchers used BaEVRLess-pseudotyped lentiviral and retroviral vectors to deliver therapeutic genes into mobilized humanized mice, achieving stable, polyclonal reconstitution and targeted globin gene editing.
• The result: This approach resulted in therapeutically relevant gamma-globin induction (61.5%) and stable HSC gene marking, paving the way for less invasive, scalable gene therapies for SCD.