Q.What is gene therapy? Illustrate using the example of adenosine deaminase (ADA) deficiency.

Gene therapy is a method to correct a gene defect that causes a disease. It involves introducing a functional gene into a person's cells and tissues to compensate for the non-functional gene.

Adenosine deaminase (ADA) deficiency is a genetic disorder caused by the deletion of the gene for the enzyme adenosine deaminase, which is crucial for the immune system. Its absence leads to severe combined immunodeficiency.

• Traditional treatments include enzyme replacement therapy, where functional ADA is injected, and bone marrow transplantation. These are not permanent cures.
• In gene therapy, lymphocytes are isolated from the patient's blood, and a functional ADA cDNA is introduced into them using a retroviral vector.
• These genetically engineered lymphocytes are then returned to the patient. …

Gene therapy represents a revolutionary approach in biotechnology, aiming to correct genetic defects that underlie various diseases. Instead of treating the symptoms, gene therapy seeks to address the root cause by introducing a functional gene into a person's cells or tissues to compensate for a non-functional one. This technique leverages the principles of genetic engineering to deliver therapeutic genes, offering the potential for long-term or even permanent cures for inherited disorders.

One of the most significant early successes and a classic example of gene therapy is its application in treating adenosine deaminase (ADA) deficiency. ADA is an enzyme critical for the proper functioning of the immune system. Its deficiency leads to a severe condition known as Severe Combined Immunodeficiency (SCID), where the patient's immune system is severely compromised, making them highly susceptible to infections. This deficiency is caused by the deletion of the gene responsible for producing the ADA enzyme.

Before gene therapy, the primary treatments available for ADA deficiency included:

• Enzyme Replacement Therapy: In this method, the patient is given regular injections of the functional ADA enzyme. While it provides temporary relief and improves immune function, it is not a permanent cure and requires continuous administration.
• Bone Marrow Transplantation: This involves transplanting healthy bone marrow cells from a compatible donor into the patient. If a suitable donor is found, this can be a more effective treatment, but finding a match is often challenging, and there are risks associated with the procedure.

The first gene therapy to treat ADA deficiency was performed in 1990 on a 4-year-old girl. The approach involved the following steps:

• Isolation of Lymphocytes: Lymphocytes, a type of white blood cell, were isolated from the patient's blood.
• In Vitro Culture: These lymphocytes were then grown in a laboratory culture.
• Gene Introduction: A functional ADA complementary DNA (cDNA) was introduced into these cultured lymphocytes. This was typically done using a retroviral vector, which acts as a vehicle to carry the functional gene into the cells.
• Reintroduction to Patient: The genetically engineered lymphocytes, now capable of producing ADA, were then returned to the patient's body. …

Method — define, then map the definition onto the ADA case

Definition: gene therapy = insert a functional gene to compensate for a non-functional one.

Map onto ADA: the missing/faulty gene is the one for adenosine deaminase → its absence causes SCID → the fix is to give the patient's own lymphocytes a working ADA gene (via a retro …