Why does gene therapy using engineered mature T-lymphocytes for ADA deficiency require periodic, repeated infusions rather than providing a permanent cure?
Answer and explanation
Correct answer: A. Because mature human T-lymphocytes are mortal and have a finite lifespan in the blood
- Step 1: In the lymphocyte infusion procedure, mature circulating T-cells are harvested and transduced in culture.
- Step 2: Fully differentiated mature lymphocytes are somatic cells with a natural lifespan of a few months.
- Step 3: When these cells undergo apoptosis, the therapeutic gene is lost, requiring lifelong periodic infusions; a permanent cure can only be achieved if the functional gene is introduced into immortal pluripotent hematopoietic stem cells at early embryonic stages.
Answer
Because mature human T-lymphocytes are mortal and have a finite lifespan in the blood.
Why not the others: The retroviral vector stably integrates as a provirus and does not continuously mutate; Patients do not reject the self-antigen enzyme; Integrated proviruses replicate with host DNA and are not degraded.
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