Question
What is gene therapy? Explain how ADA (adenosine deaminase) deficiency is treated using gene therapy. Why is this treatment not a permanent cure in many cases?
(NCERT Class 12 — directly asked in NEET and CBSE boards)
Solution — Step by Step
Gene therapy is a technique that involves inserting a functional copy of a gene into a patient’s cells to correct a genetic disorder. The idea is simple — if a gene is defective, supply a working copy.
It can be done on somatic cells (affects only the patient, not inherited) or germ cells (heritable — currently not permitted in humans due to ethical concerns).
ADA (adenosine deaminase) is an enzyme needed for the normal functioning of the immune system. Without ADA, toxic metabolites (deoxyadenosine) accumulate and destroy lymphocytes.
Children born with ADA deficiency suffer from Severe Combined Immunodeficiency (SCID) — they have virtually no functional immune system and can die from even minor infections.
- Isolate lymphocytes from the patient’s blood
- Clone the functional ADA gene into a retroviral vector
- Infect the patient’s lymphocytes with the recombinant retrovirus in the lab — the virus inserts the functional ADA gene into the lymphocyte DNA
- Grow the genetically modified lymphocytes in culture
- Reinfuse them back into the patient
The corrected lymphocytes now produce ADA and function normally.
The lymphocytes have a limited lifespan. As the corrected lymphocytes die, the patient needs repeated infusions of genetically engineered lymphocytes.
For a permanent cure, the gene would need to be introduced into bone marrow stem cells (which continuously produce new lymphocytes). Early-stage stem cell gene therapy has shown promise, but it carries risks including insertional mutagenesis (the retrovirus might integrate near an oncogene and cause cancer).
An alternative treatment: regular injections of synthetic PEG-ADA (polyethylene glycol-modified ADA enzyme) — this is not gene therapy but enzyme replacement therapy.
Why This Works
Gene therapy for ADA deficiency was the first approved gene therapy trial in humans (1990, Ashanti DeSilva). It worked because the disease is caused by a single gene defect, and the target cells (lymphocytes) can be easily collected, modified, and returned.
Retroviruses are used as vectors because they naturally integrate their DNA into the host genome — exactly what we need for long-term gene expression. The trade-off is the risk of random integration that might disrupt important genes.
Alternative Method — Comparison of Treatments
For NEET, know all three treatment approaches for ADA deficiency:
| Treatment | Type | Permanent? |
|---|---|---|
| Gene therapy (lymphocytes) | Gene correction | No — needs repeated infusions |
| Bone marrow transplant | Cell replacement | Yes — if donor match found |
| PEG-ADA injection | Enzyme replacement | No — lifelong injections needed |
NEET often asks why gene therapy for ADA is not permanent — the answer is that lymphocytes have a finite lifespan and need to be periodically replaced.
Common Mistake
Students often confuse gene therapy with gene editing (CRISPR). In classical gene therapy, a new copy of the gene is added — the defective gene remains in place. In gene editing, the defective gene is corrected in situ. NCERT discusses the classical approach (adding a gene via retroviral vector). Don’t mention CRISPR in NEET answers unless the question specifically asks about it.