Question

Name the deficiency for which first clinical gene therapy was given. Mention the cause of and one cure for this deficiency.

Answer 1

Hint: Process of inserting genes into cells to treat diseases is called gene therapy. The first apparently successful gene therapy was started on September,14990 . Patient Ashanthi DaSilva was only 4 years old and had a very rare recessive hereditary disease adenosine deaminase deficiency (ADA).

Complete answer:
1. First gene therapy was given for the disease SCID. .It is the most severe congenital immunodeficiency in children is called primary immunodeficiency. It is a rare inherited immune disorder associated with T lymphocytes and (to a lesser extent) B lymphocyte dysfunction. T lymphocytes are essential to immunity. This disorder is caused due to deficiency of ADA. ADA helps conserve purines while breaking down nucleic acids and is a household enzyme that is synthesized in a wide variety of cells. System. As a result, patients with ADA develop severe combined immune deficiency.
This severe disorder is well suited for gene therapy for many reasons: The ADA gene is small and has previously been cloned and examined in detail; The target cells are T cells, which are readily available and easy to cultivate, and allow ex vivo gene therapy.
2. Cause of the disease: It is the most severe congenital immunodeficiency in children is called primary immunodeficiency. There are no B cells or T cells. SCID is caused by a recessive gene mutation that causes a deficiency in the enzyme adenosine deaminase. Consequently, SCID is characterized by a very low thymocytes count. These children are so susceptible to various infections that they live in an environment free of microorganisms.
Cure of the disease- There many different types of treatments available for ADA deficiency . Indeed, the treatment of choice is bone marrow transplantation from a perfectly HLA-matched sibling donor, which provides a cure in about eighty percent of cases. Enzyme replacement therapy, consisting of weekly intramuscular injections of ADA conjugated to polyethylene glycol (PEG) is also an alternative to Bone marrow transplantation. PEG stabilizes the ADA enzyme, allowing it to survive and function in the body for days.
Gene therapy: Now let’s understand Steps involved
A plasmid vector carrying proviral DNA was selected. Part of the proviral DNA was replaced by the ADA gene and the gene coding for antibiotic resistance and then cloned. The antibiotic resistance gene helps in selecting the clone you want with the ADA gene.
These cells were transfected with the ADA gene, exposing billions of retroviruses carrying the gene. Genetically engineered lymphocytes were implanted in culture to confirm ADA gene expression and returned to the patient.
These lymphocytes continue to circulate and synthesize ADA, increasing the patient's ability to produce antibodies.

Note: Lymphocytes have a short life span (live only a few months), so frequent transfusions are required. Inevitably, however, enzyme replacement therapy does not provide full immune reconstitution and so life expectancy is still likely to be shortened (T cells are required for mounting effective immune responses against invading micro­organisms, and in preventing cancer).
In , the ADA gene was transferred to stem cells from the umbilical cord blood during baby birth. The modified cells were returned to the baby four days after birth. This creates a constant population of cells that produce the ADA gene and therefore increase the patient's ability to produce antibodies.