Gene Therapy For Thalassemia Needs To Be Safer

Insertional oncogenesis is an inherent risk of lentiviral vectors because they are able to integrate into thousands of loci within the genome. Bluebird’s Lenti-D integrated into 1 or more oncogenes in nearly all 67 trial subjects with cerebral adrenoleukodystropy; 3 developed malignancy. The synthetic promoter that drives Lenti-D’s ubiquitous expression is culpable. BB305 is constructed with the natural, erythroid specific β-globin promoter, and has not caused malignancy or clonality in 63 with thalassemia or, on detailed analysis, in 50 with sickle cell. Michel Sadelain developed β-globin vector TNS9 in 2000, and in 2021 still believed that a safe and effective genetic cure for thal and sickle cell disease “remains to be achieved”.