Many of you may have heard about the hype around gene therapy that started around 20 years ago when experiments began. But what has actually happened? Well it turns out, until recently, not much.
Gene therapy is the process of using gene alterations to help treat diseases. This means that a patient’s cells can be extracted, genetically changed and then re-implanted where they will hopefully take effect. This has obvious benefits in terms of treating the actual cause of disease rather than just alleviating symptoms, which is what many treatments for genetic disorders currently do. While this sounds like a miracle cure for genetic diseases, there are lots of factors to consider before it can actually be achieved.
Firstly, this treatment is only suitable for gene disorders where only one or very few genes are defective. One of the most astonishing examples of successful gene therapy is to treat “bubble boy” disease, or severe combined immunodeficiency (SCID), which would require a totally sterile environment, or bubble, in order for the sufferer to survive. David Vetter (shown below) was the first ‘boy in a bubble’ that captured the attention of the public and made the condition well known.
While gene therapy has been slow in starting, it now holds a lot of promise after several different diseases have been successfully treated. SCID was the first disease that was attempted to be treated with gene therapy 20 years ago, and although it overcame the immune deficiency, some of the patients then developed leukaemia and so the trial was stopped.
We now know that the huge problem with this technique, of ‘infecting’ the patients with a viral vector, is that it was almost random in how it was inserted, and therefore had the potential to interrupt the cell function and induce cancerous abilities. However what we now have is the ability to insert genes accurately into our desired location and therefore prevent gene disruption, which is assumed to be the cause of the leukaemia in the first trial.
One new technique that has recently been used to cure (well, so far) acute lymphoblastic leukaemia in a one year-old child is TALENs, which is a tool used to cleave specific sites in the DNA and what allows for the high level of accuracy in the newer treatments. This is a huge breakthrough, and means that young children with this aggressive form of leukaemia, who are usually resistant to the standard chemotherapy and bone marrow transplant treatment, have a fighting chance of survival.
TALENs works by using a complementary strand of DNA to bind to the specific targeted site, and then uses an endonuclease protein to cause a double strand break. This means that we can insert or delete a gene by adding engineered homologous DNA which is used by our repair system to fix the break, much in the same way that the newer and more efficient method CRISPR works, which is currently being developed to replace methods such as TALENs.
In the case of this child, TALENs was used to disable two different genes. These genes are both present in the donor T cells that were injected into the child, allowing a normal immune response against the cancer to occur. The first gene edited was one that codes for a receptor on the cell marking it out as foreign from the other cells in the body, the deletion of which meaning that the T cells would not attack all of the cells in the patient, only the cancerous cells. The second gene modified allowed the T cells to evade attack from the immune-system destroying drugs that are given to leukaemia patients.
While it has been successful in this instance, the progress of gene therapy is still a little stilted, the main issue being the extreme difficulty of altering a gene in a cell and then for it to keep working. As well as this financial motivation has to be considered, is there much profit to be made from curing a rare disease? If not who will pay for the research and development of the treatment?
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