CRISPR/Cas9-Edited Gene Therapy for Sickle Cell Disease

Gene therapy remains an attractive option for cure of sickle cell disease (SCD), as the disease is caused by a single point mutation in the beta-globin gene. This industry-funded phase 2/3 interventional study evaluated the safety and tolerability of OTQ923 — an autologous, ex vivo, CRISPR/Cas9-edited, CD34+ cellular product — in the treatment of SCD. OTQ923 prevents the fetal-to-adult hemoglobin switch by inhibiting the interaction of transcription factors with regulatory elements in the γ-globin promoters (HBG1/HBG2) that are responsible for this switch.

Three young adults with severe SCD received standard-of-care treatment with hydroxyurea and red cell exchange prior to receiving a single infusion of OTQ923. Follow-up ranged from 6 to 18 …