Biomedical research

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Basics

In this section you can find answers to frequently asked questions about Gene Therapy.

Biomedical research currently receives much attention from business, scientists and the media. Major 'breakthroughs' are reported daily and scientific developments are moving fast. Gene therapy is a promising technique in the world of life sciences. But is gene therapy hype or does it already exist right now?

1. What is the basis of gene therapy?
2. Does it run in the family?
3. How does the new gene reach its proper destination?
4. Why is gene therapy an object of discussion?
5. What does the future offer us?

 


 

1. What is the basis of gene therapy?

Proteins have a lot of important functions in our body. For example, they function as building blocks, they transfer messages and break down waste materials. The blueprints of proteins are written in our genetic material, the DNA.

We call these blue prints 'genes'. When something's wrong with a blue print, or gene, properly functioning proteins cannot be produced. They work less, or not at all. This can have far reaching effects. Illnesses like haemophilia (an hereditary disorder of blood clotting) and cystic fibrosis are examples. The idea with gene therapy is that when genes contain certain faults, we should be able to do something about it. When we replace or repair the gene, this should make things right.


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2. Does it run in the family?

You inherit many things from your parents including some of your features such as eye colour and hair colour, it is often said that these things 'run in the family'. When we look at inherited characteristics such as these it's not only genes that play a role, but also a persons lifestyle choices. For example a person can have a lot of talent for playing the piano. But if this person never takes lessons, it would be very hard for them to become the second Beethoven.


Multifactorial
This is the same for a lot of diseases and disorders. In most cases it's not only your genes that determine whether or not you will become ill. It also depends on what you eat, how much exercise you have, where you live and what you go through in general. Many genetic conditions are what we call, multifactorial, meaning there are many different things both genetic and environmental that affect a person’s chances or risk of being affected. However for some diseases it is certain that you will get them, when you have a faulty gene for a certain protein. It is diseases like this that scientists hope to cure with gene therapy.

 

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3. How does the new gene reach its proper destination?

But how do we get the new gene to the right destination in the cells' DNA?  For example, in CF one of the faulty genes is in the lungs. In order for the gene to work, the replacement gene needs to get to the lungs. To do so, we need a vehicle: the gene cannot travel there on its own. Viruses are often used as a transportation vehicle. Viruses naturally deliver their own genes in cells, which can sometimes make you ill.

Cripled viruses
The viruses that are used for gene therapy are made harmless by scientists. They replace the viral genes that cause disease with the genes that need to be delivered. These modified viruses do not make you ill, but they are able to deliver the gene to the right place in the DNA.

Back to basics
In practice, this has been a bit more complicated than was originally thought. In one research project, investigating gene therapy for a severe immune disease, the gene was sometimes delivered to the wrong spot. This resulted in three patients developing leukaemia. Two of whom fortunately recovered and for the rest of the patients on the trial the therapy worked well.

They can now live normal, healthy lives without medication. Nevertheless, the risk of developing leukaemia was so great that research into gene therapy was set back quite a few years. Scientists had to pay more attention to the basics of the therapy in order to make it safer for future patients.

Knowledge and possibilities increase
In recent years better modified viruses were investigated, viruses which were more stable and able to transport and deliver genes more precisely. Scientists now claim they have safer transportation methods for certain diseases.

People are now yearning for the results of new research programmes. The first results that can give perspectives on a cure, are expected for haemophilia, cystic fibrosis, some immune diseases, metabolic disorders, eye diseases and also cancer.

 

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4. Why is gene therapy an object of discussion?

Some people think that genetic material should not be modified under any circumstances, even if this research has the potential to find a cure for many long term and potentially fatal conditions. For those who stand to benefit from the results of gene therapy research it means that their health could be improved dramatically. For many of the conditions being researched for gene therapy there are no treatments at present.

 

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5. What does the future offer us?

At the moment gene therapy has the potential to be very useful when a disease is caused by an error in one gene e.g. conditions such as Cystic Fibrosis and Chronic Granulomatous Disease. However, a lot of genetic disorders exist as a result of errors in multiple genes (sometimes hundreds of genes) and for other genetic conditions, the chance of becoming ill also depends on a person's lifestyle. In those cases gene therapy is very complicated, if not impossible, because it only works to correct one faulty gene.

Bone marrow stem cells
Other research groups focus on adding genetic material to bone marrow stem cells in order to make transplantation more safe. These stem cells, which reside in the bone marrow, are uniquely capable of generating an entirely new blood cell production and immune system when transplanted. Bone marrow stem cells are close to ideal targets for gene therapy:

  • Inherited diseases that affect blood cell production and the immune system together are among the most common inherited diseases of humans
  • Bone marrow stem cells can be easily obtained and transplanted
  • Bone marrow stem cells and their progency come everywhere in the body, thereby delivering their products, which means that also diseases that do not directly affect blood cells may be approached by stem cell gene therapy

Bone marrow stem cells are rare and occur in a frequency of 1 per 100,000. Although purification of stem cells in experimental settings has been possible, in practice they are not enriched further than approximately 100-fold. This means that the vehicle for gene transfer should be highly efficient and preferably selective for stem cells.

Efficient vehicles for gene transfer are certain classes of viruses, the retroviruses, which are capable of delivering healthy genes to the genome of diseased cells. Researchers are focused on increasing the efficiency and improving the safety of these vehicles, which is a prerequisite for clinical gene therapy. To develop gene therapy, other hurdles are addressed as well, such as:

  • The quality of the repaired blood stem cells, in other words, are these cells still capable to provide a life long active blood cell and immune system?
  • The possible immune reactions against the transgene product
  • Engraftment and production of gene modified cells in case the transgene product does not confer a natural selective advantage

What the future will bring us is hard to say. Expectations are high. The results so far are very promising, developments are coming quickly. Gene therapy offers hope for novel treatment of a variety of acquired and inherited diseases.

However, much research, development and trials are needed to translate the basic principles of gene transfer into practical and safe treatment regimens.

 

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