For the public
Introduction to the problem
Many of us will know a friend or colleague who suffers from a debilitating disease such as diabetes, the blood clotting disorder haemophilia or a muscle wasting dystrophy. Technically, it is more appropriate to refer to diseases that arise because of some genetic predisposition as medical conditions as they are acquired because of changes to our genetic material and not from infection agents, such as bacteria.
Yet, however we classify these illnesses there is no doubt that many are extremely difficult to live with, and some, in severe cases, can be life threatening.
Muscular dystrophy is an example of what is known as a monogenic disorder in essence this means that the condition arises because of a defect in a single cellular protein. The correct function of the protein is compromised. A bad protein arises, generally, because of mutations that is genetic changes in the gene from which it is made. Genes provide our genetic blueprint. This genetic code of about 30,000 genes is built from the genetic material - DNA and packaged into chromosome. A typical human chromosome has about 150 million base pairs if DNA. Most cells in our bodies have 46 chromosomes chromosomes come in pairs, with 1 copy of each pair from our mother and father. Chromosomes can only be seen at a special time of the cell cycle when a cell is dividing. For most of the time they are unfolded and held together inside the cell nucleus examples of the appearance of the cell nucleus and chromosomes from a human white blood cell are shown in this figure.
What can science do?
In principle, it is possible to correct genetic defects by putting a normal copy of the defective gene into the affected cells. The normal gene will then be decoded to make a fully functional protein, which, with luck, will allow the previously defective cells to recover full biological activity.
While this sounds easy, it is important to realise that the process is nothing like repairing a broken component in say a car. All of the cells in our body and we have more than a million million of them are inconceivably complex and have evolved over hundreds of millions of years to function as they do now. The factors that regulate the expression of each gene in particular cells are often very difficult to define. And many of these factors might be impossible to reproduce with precision using the knowledge that we have at present.
Nevertheless, over the past 15 years massive progress has been made towards the hope of performing genetic correction by gene therapy.
These web sites provide interesting insights and recent developments:
- http://www.advisorybodies.doh.gov.uk/genetics/gtac/links.htm
- http://www.kumc.edu/gec/support/grouporg.html
- http://www.bsgt.org/
- http://www.scid.net/
- http://www.genome.gov/Education/
Why EPI Vectors?
A really big problem in performing gene therapy is that the correcting gene is often copied into protein rather inefficiently in the target cells. More worryingly, the expression is commonly maintained for only a short time. Scientists have developed vector systems to overcome this the lentivirus system that was used by the French and North American groups to treat SCID kids actually maintains expression by becoming a fixed part of the genetic material technically speaking, the vector is said to integrate into the cells' chromosomes. Yet, while this gives a good result in terms of treating the condition, the side effects of integration can potentially lead to cancer.
EPI vector sets out to design gene therapy systems that are efficient but more importantly safe. Unlike the major systems that are being used at present, our system will use only components of human origin. This will prevent any complications from using DNA or proteins from viruses. Also, our system will not disrupt the host chromosomes, but instead provide a vector that mimics their behaviour. This will be a difficult task and our success depend on a detailed knowledge of the way human cells work to regulate the decoding of their genetic material.