What is Gene Therapy?

Gene therapy is a term used to describe the delivery of nucleic acid polymers (either DNA or RNA) into a patient’s cells as a drug to treat disease, including the replacement of a mutated gene with functional copy.

Gene Therapy Techniques

Gene therapies can be delivered by a number of different mechanisms (Figure 1) and introduced into either somatic (body) cells where the effect is not passed onto the children or into the gametes (sperm or egg cells) where the effect is heritable.

Here is a link to a PDF version of Figure 1 in case you find this figure difficult to read.

Figure 1: Gene therapy techniques Click to expand
_{© St George’s, University of London}

Gene Vectors

In order to get the therapeutic section of RNA/DNA/gene into the cell, a vehicle or vector is required.

Commonly used vectors include viruses, bacteria or plasmids. The vector carries the nucleic acids across the cell membrane, cytoplasm and into the nucleus of the cell.

Once inside the nucleus, the new nucleic acids may replace the function of a mutated gene, inhibit the production of a gene/protein or target sub-groups of cells for destruction (Figure 1).

Gene Therapy Potential

For many years gene therapy has promised to transform the management of patients with genetic diseases but, sadly, consistent, reliable gene therapies remain elusive. This failure of gene therapies to become a mainstay of treatment is due to a number of different factors:

• It can be challenging to ensure the nucleic acids reach the right cell at the right time. If a new gene reaches the wrong cell not only will the therapy fail but it may cause serious side effects.
• The new nucleic acids may be recognised by the body’s defence mechanism as foreign and be destroyed. As well as eliminating the therapeutic vector, the triggered immune response may cause serious clinical problems for the patient.
• It is difficult to ensure that newly introduced nucleic acids only interfere with the mutated gene and not other, normally functioning, genes.
• So far, gene therapy is enormously expensive.

Although, because of these challenges, gene therapy remains a largely experimental technique, there have been some successes including the treatment of X linked severe combined immune deficiency (SCID).

Talking point

Scientists have recently reported in the New England Journal of Medicine that they have “cured” a boy with sickle cell anaemia using gene therapy. This has been heavily reported in the mainstream media.

What are your thoughts about whether this is a “game-changer” for the field and why?