Genetic Technology: Question 9

Worked solution

Part (a): Delivering the functional gene into bone marrow stem cells

Because lymphocytes are continuously produced from bone marrow stem cells, correcting the fault in these stem cells allows the correction to be passed on to newly made lymphocytes.

1. Bone marrow stem cells are removed from the child’s body.
2. A functional copy of the gene is inserted into a vector, most commonly a virus that has had its own harmful, disease-causing genes removed so that it can no longer cause illness but can still enter cells.
3. This vector is used to introduce the functional gene into the bone marrow stem cells in the laboratory; the gene becomes incorporated into the DNA of these cells.
4. The genetically modified stem cells are then returned to the child, usually by infusion back into the bone marrow, where they can continue to divide.

Because the functional gene is now present in these dividing stem cells, lymphocytes subsequently produced from them also carry and express the functional gene, allowing the child’s immune system to develop and respond to infection more normally.

Part (b): Problems limiting long-term success

Problem 1. The effect may not be permanent. For the correction to last, the functional gene needs to be incorporated into cells that behave as true, self-renewing stem cells, continuing to divide and produce a fresh supply of corrected lymphocytes indefinitely. If the gene is instead incorporated into cells with more limited capacity to divide, the number of corrected cells (and the lymphocytes derived from them) declines over time as they die and are not fully replaced, so the benefit of the treatment can fade and further rounds of treatment may be required.

Problem 2. An immune response against the vector. The viral vector used to deliver the gene, or proteins associated with it, can be recognised by the patient’s own immune system as foreign. This immune response can reduce how effectively the vector delivers the gene, and can make a second or later treatment with the same type of vector less effective (because the immune system now recognises and attacks it more quickly) or carries an increased risk of a harmful immune reaction.

(An equally acceptable second problem: because the vector’s genetic material can insert into the patient’s genome at a more or less random position, there is a risk that it disrupts a gene that normally controls cell division, such as a tumour-suppressor gene. If this happens, the affected cell may begin to divide uncontrollably, which has, in some real gene therapy trials for SCID, led to leukaemia in a small number of patients.)

Final answers

• (a) A functional copy of the gene is carried by a modified viral vector into bone marrow stem cells removed from the child; the corrected stem cells are returned to the child’s bone marrow and divide to produce lymphocytes that express the functional gene.
• (b) Two acceptable problems: the effect can fade if the gene is not incorporated into true self-renewing stem cells so corrected cells are not continuously replaced; and the patient’s immune system may respond against the viral vector, reducing effectiveness and limiting repeat treatment (or: random insertion of the vector’s DNA can disrupt a gene controlling cell division, risking cancer).