The Triumphs and Challenges in Gene Therapy

17 February 2015
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Gene therapy is the treatment of a disease by replacing or altering a gene that is abnormal and whose abnormality is responsible for the disease. It can also supplement genes that are completely absent.

When a gene is abnormal or absent, the product for which it is supposed to be a blueprint (its ‘expression’) will be faulty, absent or even do the exact opposite of what it is supposed to do. This can cause cells to either malfunction, function too well or do things that they’re not supposed to do, causing diseases like blindness, auto-immune disease and cancer.

By successfully introducing the corrected gene into the human cells, such diseases may be treated or even cured. Besides correcting faulty genes, gene therapy can also be used to deliver genes that speed up the destruction of cancer cells, deliver bacterial or viral genes as a form of vaccination or provide genes that stimulate healing of damaged tissue.

Delivery Methods

Delivering genes is easier said than done, of course. The human body doesn’t really like the introduction of ‘foreign’ material. Our immune system is made to neutralise unknown bodies, which means that simply injecting the corrected cells and hoping for the best won’t be very effective; the altered genes need to be delivered into the patient’s cells and subsequently incorporated into the genetic material of those cells. Unfortunately, penetrating a human cell without destroying it altogether is the next major hurdle to take.

However, there is a type of organism that is exceptionally good at this: viruses. Viruses attach themselves to a host cell, inject their genetic material into it and then use the cell’s copy function to make copies of themselves. As a bonus, they usually also bypass the immune system until they have done this, making them an almost ideal transportation method (The word ‘almost’ is used because the viruses have to be made innocuous first, of course, otherwise the patient would not only receive gene therapy but be infected with the virus as well).

Genes can also be delivered within tiny envelopes of fat molecules. As cell membranes contain a very high concentration of fat molecules, the envelope can carry the altered gene into the cell by pretending to be one of the cell’s own molecules.


The concept of gene therapy isn’t new. In 1970, Stanfield Rogers, an American doctor theorised that ‘good DNA’ could be used to replace defective DNA in patients with genetic disorders, and tried this idea out on two sisters who were suffering from a genetic disorder called argininemia. His attempt was unsuccessful.

In 1972, Theodore Friedmann and Richard Roblin published a paper in Science called, ‘Gene therapy for human genetic disease’, referring to Rogers and urging himto proceed with caution.

It wasn’t until 1990 when the first actual gene therapy was performed on a human: a four year old girl at the NIH Clinical Centre in Bethesda, Maryland, suffering from a congenital disease called adenosine deaminase (ADA) deficiency was given corrected genes using her own white blood cells.


Although gene therapy has shown promising results in clinical trials, governments are hesitant to allow commercialisation of these therapies, mainly because of poor and sometimes lethal results in the 1990s as well as ethical pressure.

Gene TherapyWhen gene therapy is administered to a single individual and targeted to specific cells of that individual, the effects are confined to this one person. This is called somatic gene therapy. However, when not only an individual’s body cells are altered, but also his or her reproductive cells (gametes), the gene therapy leads to heritable alterations in the genome that is then passed on to future generations. This is called germline therapy and this has raised a whole catalogue of ethical concerns about the possible implications of altering genes.

Although germline therapy could counteract hereditary diseases, many countries prohibit its use due to a lack of knowledge about its long-term effects and fear over unknown risks for future generations.

Somatic gene therapy has fewer ethical issues compared with germline gene therapy, but is merely still in its early stages of design and is continuing to face unsolved technological problems, including:

  • The relative short-lived effect of the therapy, calling for repeated treatment. (Human cells divide rapidly; unfortunately, faulty cells are no exception);
  • The complexity of many diseases: lots of diseases are caused by not one defective gene but a combination of altered or dysfunctional genes, making them difficult to treat;
  • The body’s immune system, which is designed to fight off any unknown DNA. Insertion of altered cells can trigger toxic, allergic or inflammatory reactions and repeated therapy increases the chances of the body’s immune system recognising foreign bodies, disrupting the effectiveness of the therapy as a whole.

Use of viral vectors such as the transport mechanism to deliver the corrected DNA even carries the risk of the virus recovering its ability to cause disease once it has penetrated the target cells. There is also a risk of inducing tumour growth, when the inserted DNA is incorrectly placed.

The ‘Bionic Chip’

A relatively new method is gaining access to a cell by applying an electrical charge to create tiny openings in the cell’s membrane. This technique is called electroporation and is potentially extremely precise because it allows doctors to target specific groups of cells, rather than any set of cells.

Rubinsky and Huang, two engineers at the University of California at Berkeley, discovered that cells acts like diodes, passing or blocking electricity at specific voltages. They built a single living cell into an electronic chip and when it was hit with just the right charge, the cell membrane opened, allowing the electricity to pass from the top to the bottom of the bionic chip. By recording what voltage caused this phenomenon to occur, it is now possible to determine precisely how much electricity it takes to pry open different types of cells.

As new technologies such as this ‘bionic chip‘ are developed further , and the technological problems mentioned above are solved, it is very likely that gene therapy will play an increasingly important and prominent part in medicine in the decades to come.


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Dagmar Ottevangers

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