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

Phagocytosis-shielded BaEVRLess-pseudotyped lentiviral vectors achieve up to 8.8% gene marking in humanized mice, with chemoselection enriching to 70% of HSCs for SCD therapy.

• Why it matters: Current ex vivo HSC gene therapy for sickle cell disease requires complex procedures, limiting accessibility; in vivo delivery could simplify treatment and expand patient access.
• What they did: Researchers used BaEVRLess-pseudotyped lentiviral vectors to deliver genes directly into mobilized humanized mice, achieving stable, polyclonal reconstitution and targeted gene editing with miRNA-embedded shRNAs.
• The result: This approach enabled therapeutically relevant gamma-globin induction, with 61.5% of beta-like globins, demonstrating that in vivo gene transfer with these vectors can support fetal globin induction for SCD.