9 min readPathway sheetOften a 3-mark answer on gene therapy for ADA deficiency; 1-mark MCQ or assertion-reason; also a NEET favourite

Gene therapy: the ADA deficiency case

Gene therapy corrects a gene defect by delivering a normal gene. The first, in 1990, treated ADA deficiency by putting functional ADA cDNA into the patient's lymphocytes.

Gene therapyMethods to correct a gene defect diagnosed in a child or embryo, by putting a normal gene into the person's cells or tissues

First clinical gene therapy1990, a 4-year-old girl with adenosine deaminase (ADA) deficiency

ADA deficiencyCaused by deletion of the gene for adenosine deaminase, an enzyme crucial for the immune system

VectorA retroviral vector carrying functional ADA cDNA

What gene therapy is

If a person is born with a hereditary disease, gene therapy tries to correct it. It is a set of methods for correcting a gene defect diagnosed in a child or embryo. A normal gene is delivered into the person's cells or tissues. It takes over the function of the faulty gene and makes up for it.

ADA deficiency

The enzyme adenosine deaminase (ADA) is crucial for the immune system to work. ADA deficiency is caused by the deletion of the gene for ADA, so the child's immunity fails. cDNA (complementary DNA) is a DNA copy made from the gene's mRNA, so it carries just the coding sequence.

Treatments for ADA deficiency

Treatment	What is done	Limitation
Bone marrow transplantation	Healthy marrow from a donor is given	Not completely curative
Enzyme replacement therapy	Functional ADA is given by injection	Not completely curative
Gene therapy with lymphocytes	The patient's lymphocytes get functional ADA cDNA and are returned	Cells are not immortal, so infusions must be repeated
Gene therapy at an early embryonic stage	The ADA gene from marrow cells is put into cells at an early embryonic stage	Could give a permanent cure

Gene therapy for ADA deficiency

1
Lymphocytes (a type of white blood cell) are taken from the patient's blood.
2
They are grown in a culture outside the body.
3
Functional ADA cDNA is introduced into them using a retroviral vector.
A disarmed retrovirus carries the gene into the cells
4★
The genetically engineered lymphocytes are returned to the patient.
5★
These cells are not immortal, so the patient needs periodic infusions.

★ key step

In real life

Sickle cell anaemia and thalassaemia affect many families in India. Gene therapies for these inherited blood disorders are now being developed and tested. They follow the same idea: give the patient's cells a working gene.

Exam angle

3 marks: “Describe the gene therapy given to a patient with ADA deficiency. Why is it not a permanent cure?” Lymphocytes taken from the patient's blood, grown in culture; functional ADA cDNA introduced with a retroviral vector; cells returned to the patient. Lymphocytes are not immortal, so periodic infusions are needed. A permanent cure would need the gene in early embryonic cells.

2 marks: “What is the role of adenosine deaminase? Name two treatments for its deficiency other than gene therapy.” It is crucial for the immune system to work. Bone marrow transplantation and enzyme replacement therapy (ADA by injection).

1 marks: “Name the vector used to deliver ADA cDNA into lymphocytes.” A retroviral vector.

Remember it

ADA therapy: Out, Grow, Add, Return, Repeat: lymphocytes out, culture, retrovirus adds ADA cDNA, cells back, repeat infusions.