A Novel CRISPR-Cas9 Approach Targets Fetal Hemoglobin to Alleviate Sickle Cell Disease
A recent study utilizes CRISPR-Cas9 gene editing technology to modify fetal hemoglobin expression in hematopoietic stem cells, demonstrating promising outcomes for severe sickle cell disease. The treatment known as OTQ923 has the potential to be a game-changer in managing this life-threatening condition.
HCN Medical Memo
For physicians treating sickle cell disease, this study signals a notable advancement in therapeutic options. The CRISPR-Cas9 edited CD34+ cells not only showed stable engraftment but also resulted in significant clinical improvement. Adopting such gene-editing strategies could radically transform the management of sickle cell disease in your practice.
- The study employed a tiling CRISPR-Cas9 screen on HBG1 and HBG2 gene promoters in CD34+ cells from healthy donors.
- Researchers identified the most effective guide RNA (gRNA-68) to proceed with clinical development.
- Severe sickle cell disease patients were enrolled in a multicenter, phase 1–2 clinical trial to evaluate the safety and efficacy of OTQ923.
- CD34+ cells edited with CRISPR-Cas9 and gRNA-68 demonstrated sustained on-target editing and high levels of fetal hemoglobin.
- Three study participants showed successful engraftment and stable fetal hemoglobin induction, ranging from 19.0 to 26.8% of total hemoglobin.
- Manifestations of sickle cell disease decreased during the 6- to 18-month follow-up period.
The only potentially curative option for SCD is allogeneic hematopoietic stem-cell transplantation (HSCT), ideally from a human leukocyte antigen (HLA)–matched donor; this procedure is available for fewer than 20% of patients.
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