Genes are pieces of DNA that can each make an important substance, which we call proteins. These proteins make up most of our body and perform almost all of its functions. But sometimes there can be an error in the DNA. If you are unlucky, that mistake is just in an important place in a gene, so that the protein that is made does not work or works differently. In some cases this can lead to a serious illness, for example cystic fibrosis. The challenge posed by genetic disorders is that the cause is encrypted in the genome. Until recently, the only solution was lifelong medication to control the symptoms. But now we're trying to tackle disease at its source: the broken genes themselves.
Cut and paste
The fact that broken genes can be responsible for a disease also raises interesting questions. For example, can we replace a bad gene with a good one? Or adapt a bad gene so that the protein regains its original function? These kinds of questions have led to a lot of research into new treatment methods, with a few important discoveries as a result. First of all, a way had to be found to find the faulty gene in the DNA. This first milestone was reached in 1998. After that, a long time has been spent on techniques for cutting and pasting a gene. But that did not solve the most difficult question: how do you get the cutting and pasting tools in the right place?
The solution turned out to be a virus. Viruses are real experts in DNA modification. In order to multiply in a cell, viruses use an entire arsenal of proteins to copy, modify and move DNA. Normally many of these viruses are our enemy, but by adapting and weakening them in the lab they can be used in a controlled manner. These attenuated viruses are called vectors. Vectors can enter a cell and interact with DNA, but cannot propagate themselves uncontrollably. Sometimes the machinery of the virus itself is used to make repairs, but it is also possible that the virus is only used to deliver a package to cells that need to be changed. The advantage of changing a cell's genome is that it also passes the corrected genome onto daughter cells when it divides. This is particularly interesting for stem cells, which main job is to produce new cells for the body.
Bumps on the road
This all may sound quite well thought out, so why aren’t there any widespread treatments yet? One of the reasons is that the techniques sometimes turn out differently than planned when put into practice. For example, after years of research it may turn out that the particular treatment is not safe enough. But there are also more specific challenges. For example, it is very important to investigate whether the vector does not behave unexpectedly in the body. Another hurdle is that the immune system can recognize the modified virus as an invader, clearing the virus before it can do its work. That is why a lot of research is focused on this area of the treatment. Finally, there is still an open question about how these treatments should be administered in the future. Some scientists suggest spraying and inhaling the virus, while others believe that injection or ingestion might be a better method.
Repairing broken genes is a fairly classic form of gene therapy. In the meantime, a number of new types have already been thought out, for example adding a completely new gene. One of the possible uses would be to add a kind of "suicide gene", a gene that weakens or kills a cell when a protein is made from the gene. The viral vector can then be designed to bind only to specific cells, such as tumor cells. Tumor cells are cells of the body that divide uninhibited and thereby cause cancer. Instead of inhibiting all cells of the body (chemotherapy) or violently treating them locally (radiation), a viral vector could bind to the cancer cells and deliver the suicide gene. The hope is that this will lead to a cure without many side effects. There is still a long way to go for gene therapy, but the possibilities are worth the wait.