Gene Therapy

Gene therapy is an approach to treating a genetic disorder that attempts to correct the disorder at its actual source -- the defective or missing gene itself -- rather than merely managing its symptoms. In its simplest conception, gene therapy involves delivering a normal, functional copy of a gene into the cells of a patient whose own copy of that gene is defective or missing, so that the patient's cells can begin producing the protein that the defective gene failed to produce correctly.

Adenosine deaminase (ADA) deficiency is the disorder used as the classic illustrative example of gene therapy, and was in fact the condition treated in the first approved human gene therapy trial. ADA deficiency is caused by the deletion or malfunction of the gene coding for the enzyme adenosine deaminase, an enzyme essential for the normal functioning of certain immune system cells (lymphocytes). Without functional ADA enzyme, affected individuals develop severe combined immunodeficiency (SCID), leaving them extremely vulnerable to infections; historically, some ADA-deficient children could survive only inside a completely germ-free, isolated environment.

In the pioneering gene therapy approach used for ADA deficiency, lymphocytes were extracted from the patient's blood, and a functional, normal copy of the ADA gene was introduced into these lymphocytes in the laboratory (using a viral vector engineered to carry and insert the ADA gene into the cell's genome, rather than a plasmid vector). These genetically corrected lymphocytes, now capable of producing functional ADA enzyme, were then reintroduced into the patient's body by infusion.

The important limitation of this particular approach was that ordinary lymphocytes, like most differentiated blood cells, are not permanently self-renewing -- they have a limited natural lifespan and are gradually lost from the body over time. As a result, the corrected lymphocytes infused into an ADA-deficient patient would themselves eventually die out, meaning the whole procedure -- extracting cells, correcting them, and re-infusing them -- had to be periodically repeated throughout the patient's life to maintain an adequate level of functional ADA enzyme, rather than providing a single, permanent cure. …