Outline how genetic diseases can be treated with gene therapy, using the examples severe combined immunodeficiency (SCID) and inherited eye diseases

SouravNovember 1, 2024

Answer

Gene therapy is an innovative approach to treating genetic diseases by directly modifying the genes responsible for the condition. This method has shown promise in various disorders, including severe combined immunodeficiency (SCID) and inherited eye diseases. Below is an outline of how gene therapy can be applied to these conditions, highlighting its mechanisms and benefits.

Gene Therapy for Severe Combined Immunodeficiency (SCID)

1. Overview of SCID:
   • SCID is a group of inherited disorders characterized by a severe deficiency in T and B lymphocytes, leading to a compromised immune system. Patients with SCID are highly susceptible to infections.
2. Mechanism of Gene Therapy:
   • Gene Replacement: In cases of SCID caused by mutations in specific genes (e.g., IL2RG), gene therapy involves inserting a functional copy of the defective gene into the patient’s hematopoietic stem cells (HSCs).
   • Procedure:
     • Hematopoietic Stem Cell Collection: Stem cells are harvested from the patient’s bone marrow or peripheral blood.
     • Gene Editing: The collected stem cells are modified ex vivo using viral vectors (often lentiviral vectors) that deliver the healthy gene into the cells.
     • Reinfusion: The genetically modified stem cells are then infused back into the patient, where they can develop into functional immune cells.
3. Benefits:
   • Restoration of Immune Function: Successful gene therapy can restore the immune system’s ability to fight infections, significantly improving the quality of life for SCID patients.
   • Long-term Efficacy: The modified stem cells can persist in the body, providing a lifelong supply of functional immune cells.

Gene Therapy for Inherited Eye Diseases

1. Overview of Inherited Eye Diseases:
   • Inherited retinal diseases (IRDs) encompass a range of genetic disorders that lead to progressive vision loss and blindness, often due to mutations in specific genes affecting photoreceptor function.
2. Mechanism of Gene Therapy:
   • Gene Replacement Therapy: Gene therapy for IRDs often involves replacing a mutated gene with a healthy copy. For example, conditions like Leber congenital amaurosis (LCA) caused by mutations in the RPE65 gene can be treated using this approach.
   • Procedure:
     • Vector Delivery: A viral vector, such as adeno-associated virus (AAV), is used to deliver the normal RPE65 gene directly into retinal cells through subretinal injection.
     • Expression of Functional Protein: Once inside the cells, the healthy gene is expressed, allowing for the production of functional proteins necessary for photoreceptor health and function.
3. Benefits:
   • Restoration of Vision: Successful gene therapy can halt or even reverse vision loss in patients with certain IRDs. For example, clinical trials have shown that patients treated with Luxturna (the first FDA-approved gene therapy for an inherited retinal disease) experienced significant improvements in visual function.
   • Targeted Approach: Gene therapy specifically addresses the underlying genetic cause of the disease rather than merely alleviating symptoms, providing a more effective long-term solution.