What Are the Pros and Cons of Gene Therapy for SCID?

Severe combined immunodeficiency (SCID). The disease is caused by adenosine deaminase ADA deficiency or interleukin receptor (IL-2R most common) dysfunction. The former is an autosomal recessive genetic disease, and the latter is an X recessive genetic disease. Although deletion mutations were also found in ADA-encoding genes, most were base substitution mutations.

SCID

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Severe combined immunodeficiency

Severe combined immunodeficiency (SCID)

The disease is caused by adenosine deaminase ADA deficiency or IL receptor deficiency. The ADA activity deficiency disease is a recessive genetic disorder of the X chromosome. Although deletion mutations were also found in ADA-encoding genes, most were base substitution mutations.

ADA enzyme is an enzyme that can deaminate adenosine into inosine. Mutations in this gene result in reduced ADA activity and stability. Decreased ADA activity increases adenosine levels, which in turn promotes deoxyadenosine and dATP levels. Elevated dATP is toxic, especially to lymphocytes. This is because the function of ribonucleotide diphosphate reductase is to catalyze the synthesis of four kinds of deoxynucleotides as raw materials for DNA synthesis. And dATP is an inhibitor of this enzyme. Increasing dATP content will inhibit DNA synthesis in immune cells and cause abnormal development of immune cells. So under normal circumstances, lymphocytes have high activity of ADA to avoid damage. Decreased ADA activity will cause cell damage or death, causing cell humoral immune deficiency.

The patient appears to be susceptible to infection. Examination revealed a decrease in the number of peripheral blood lymphocytes (severe lymphocytopenia) and hypoimmunoglobulinemia. Erythrocytes have low ADA activity and elevated dATP levels. Decreased ADA levels confirm the diagnosis of SCID.

1. Reasonable use of antibiotics and regular injection of immunoglobulins. Bovine ADA with intramuscular injection of polyethylene glycol. Bovine ADA is relatively non-immunogenic and linked to polyethylene glycol can extend half-life. It has been shown to be effective in ADA-deficient diseases, but may reduce the effectiveness of treatment as the disease progresses.

2. Bone marrow transplantation is the best method to treat the disease.

3. Gene therapy. It is the first human disease to be treated with somatic gene therapy technology, so that many SCID patients have become a model of in vitro gene therapy.