Gene Therapy for ADA Deficiency: Steps and Limitation
Biology · Biotechnology and Its Applications · NEET
Gene therapy for ADA (adenosine deaminase) deficiency works like this: doctors take lymphocytes (a type of white blood cell) from the patient's blood, grow them in culture, insert a functional ADA gene (ADA cDNA) using a retroviral vector, and return these cells to the patient. The limitation: these lymphocytes are not immortal, so they die over time and the patient needs periodic (repeated) infusions. Memory hook: "Grow, Insert, Return, Repeat" — and a real cure would need the gene put into early embryonic cells.
The four steps of ADA gene therapy: take lymphocytes, grow in culture, insert ADA cDNA using a retroviral vector, and return the cells to the patient. Because these lymphocytes are not immortal, repeated infusions are needed, so it is not a permanent cure.
Your doubts, answered
Is gene therapy for ADA deficiency a permanent cure?
No. The lymphocytes used carry the functional ADA gene but they are not immortal, so they die after some time. Because of this, the patient needs periodic (repeated) infusion of fresh genetically engineered lymphocytes. NCERT calls this the main limitation. A permanent cure would need the ADA gene to be introduced into cells at early embryonic stages.
Why does the ADA patient need repeated infusions of lymphocytes?
Because the corrected cells are mature lymphocytes, not stem cells. Mature lymphocytes have a limited lifespan (they are not immortal). Once they die, the source of functional ADA is gone, so the patient must be given the engineered lymphocytes again and again. This exact reason was asked in NEET 2022.
Which vector is used to introduce the ADA gene into lymphocytes?
A retroviral vector (a retrovirus). The functional ADA cDNA is packed into a retroviral vector and used to carry the gene into the patient's lymphocytes. Do not confuse this with Ti plasmid (used for plants) or with pBR322 and lambda phage (cloning vectors, not used for human lymphocytes).
How is gene therapy for ADA different from bone marrow transplant and enzyme replacement therapy?
NCERT gives three treatments for ADA deficiency. (1) Bone marrow transplantation. (2) Enzyme replacement therapy — functional ADA enzyme is given by injection. (3) Gene therapy — a functional ADA gene is inserted into the patient's own lymphocytes. The first two are not completely curative; gene therapy is the attempt to correct the gene itself, but even it is not permanent unless done in early embryonic cells.
What causes ADA deficiency and what does it affect?
ADA deficiency is caused by the deletion of the gene for the enzyme adenosine deaminase. This enzyme is crucial for the immune system to function, so its deficiency causes dysfunction of the immune system (severe combined immunodeficiency). This is why NEET 2021 answer was 'dysfunction of immune system'.
⚠️ The NEET trap ✗ ADA gene therapy is a permanent, one-time cure because the correct gene is inserted into the patient. ✓ Current ADA gene therapy uses mature lymphocytes that are not immortal, so it needs periodic re-infusion; a permanent cure would require introducing the ADA gene into early embryonic cells. 🧠 NTA loves the word 'permanent'. If the exam says gene therapy in lymphocytes is a permanent cure, it is wrong — the cells are not immortal.
Real NEET questions
NEET 2016 (Phase 2)
Which kind of therapy was given in 1990 to a four-year-old girl with adenosine deaminase (ADA) deficiency?
A · Gene therapy ✓
B · Chemotherapy
C · Immunotherapy
D · Radiation therapy
Solution: The first clinical gene therapy was given in 1990 to a 4-year-old girl with ADA deficiency. A functional ADA cDNA is delivered (via a retroviral vector) into the patient's lymphocytes to make up for the deleted gene.
NEET 2018
Which of the following is commonly used as a vector for introducing a DNA fragment in human lymphocytes?
A · λ phage
B · Ti plasmid
C · Retrovirus ✓
D · pBR 322
Solution: In ADA gene therapy the functional ADA cDNA is introduced into the patient's lymphocytes using a retroviral vector. Ti plasmid is for plants; λ phage and pBR322 are cloning vectors, not used to move genes into human lymphocytes.
NEET 2022
In gene therapy of Adenosine Deaminase (ADA) deficiency, the patient requires periodic infusion of genetically engineered lymphocytes because:
A · Retroviral vector is introduced into these lymphocytes
B · Gene isolated from marrow cells producing ADA is introduced into cells at embryonic stages
C · Lymphocytes from patient's blood are grown in culture, outside the body
D · Genetically engineered lymphocytes are not immortal cells. ✓
Solution: The engineered lymphocytes are mature cells and are not immortal, so they die off. Because of this the patient must be given fresh genetically engineered lymphocytes again and again (periodic infusion).
Solved Biotechnology and Its Applications NEET PYQs
Try the real previous-year questions from this chapter — each with the answer and a full solution.
Lymphocytes from the patient's blood are taken and grown (cultured) outside the body. Then a functional ADA cDNA is inserted into them using a retroviral vector, and the cells are returned to the patient.
Why is ADA important in the body?
Adenosine deaminase is an enzyme crucial for the immune system to function. Its deficiency (from deletion of the ADA gene) causes dysfunction of the immune system, known as SCID.
What is the main limitation of ADA gene therapy?
The corrected lymphocytes are not immortal and die over time, so the patient needs periodic infusions. It is therefore not a permanent, complete cure.
How could ADA deficiency be permanently cured?
If the ADA-producing gene isolated from marrow cells is introduced into cells at early embryonic stages, it could act as a permanent cure, according to NCERT.
What are the non-gene-therapy treatments for ADA deficiency?
Bone marrow transplantation and enzyme replacement therapy (injecting functional ADA). NCERT notes that both are not completely curative.
