Marco Donia: Welcoming the Era of Gene Editing in Medicine
Marco Donia,
“Autologous Gene-Engineered Cell Therapies for Genetic Diseases: Welcoming the Era of Gene Editing in Medicine.
- Welcoming the Era of Gene Editing in Medicine (NEJM Perspective, Apr 24, 2024)
- Extending Gene Medicines to All in Need (NEJM Editorial)
- Exagamglogene Autotemcel for Transfusion-Dependent β-Thalassemia (Exa-cel for β-thalassemia)
- Exagamglogene Autotemcel for Severe Sickle Cell Disease (Exa-cel for severe sickle cell disease)
About Exagamglogene Autotemcel (exa-cel):
Exa-cel utilizes CRISPR-Cas9 technology to edit the genome of CD34+ hematopoietic stem cells extracted from patients.
These cells are engineered at the erythroid-specific enhancer region of BCL11A, enabling the production of fetal hemoglobin, which effectively replaces the defective hemoglobin that causes severe symptoms in diseases like β-thalassemia and sickle cell disease.
Key Points:
Efficacy 1: Over 90% of patients with transfusion-dependent β-thalassemia treated with exa-cel achieve complete transfusion independence for more than 12 months.
Efficacy 2: Exa-cel has been shown to eliminate vaso-occlusive crises in 97% of patients with sickle cell disease for a period of 12 months or more.
Safety: The safety profile of exa-cel is comparable to that of traditional bone marrow transplantations, with most adverse effects being manageable and transient.
Take-Home Message:
Exa-cel is a transformative, potentially curative cell-based treatment, building on technological advances of the past decade.
Challenges: high costs (exceeding $2 million), the need for prolonged hospitalization, and the requirement for high-dose chemotherapy within highly specialized centers.
How These Therapies Are Made: .
Cell Collection: Patients undergo a process where hematopoietic stem cells are harvested.
Gene Editing: These cells are then genetically modified in a lab using the precise CRISPR-Cas9 system to promote the expression of fetal hemoglobin.
Reinfusion: The engineered cells are infused back into the patient, where they engraft and start producing healthy blood cells.
Perspective: The continued development of gene-edited cell therapies holds great promise for treating a variety of diseases.
Exa-cel and Lovo-cel are FDA approved.”
Source: Marco Donia/LinkedIn
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