We are all familiar with taking conventional medicines to treat an illness or infection, relying on the efficacy of the active pharmaceutical ingredient to alleviate our symptoms and perhaps compensate for some deficiency in our body’s functioning. Yet conventional treatments can only offer temporary relief for some conditions. For many chronic illnesses, we remain dependent on taking medicines time and again, sometimes daily. But what if, instead of treating a disease with a chemical compound, we could target the disease at the genomic level? What if we could introduce new genetic material that would change the very function of our cells and provide long-lasting relief, or even a cure? This is the potential of gene therapy.
Healthy cell function relies on the production of the correct proteins in the right amounts, which is determined by our genes. A defective gene can lead to the over- or underproduction of a particular protein, leading to a seriously detrimental effect within the cell and wider body. For example, cystic fibrosis is caused by a defective CFTR gene, which does not produce enough of the protein that controls the transport of water and salt across the cell membrane. The goal of gene therapy is to correct this defect through the targeted introduction of a fully functioning gene to a patient’s cells – restoring ‘healthy’ protein production to treat the genetic root of the disease.
Usually, a copy of the functioning gene is packaged into a modified, benign viral vector that can transport the genetic material to the targeted cells. Depending on the viral vector used, it may then be incorporated into the cell’s genome, or remain free inside the cell, but still available for transcription. In the latter instance, the new genetic information is not passed on during cell division, since the genome of the cell is not permanently altered. The viral vector may be introduced directly into the body, e.g. by injection, or an ex vivo approach may be appropriate. CAR-T cell therapy an example of an ex vivo approach, where T cells – a type of white blood cell – are extracted from the patient, modified to produce chimeric antigen receptors that improve their recognition of cancer cells, then reintroduced into the body.
Gene therapy, while opening up huge possibilities, is not without its difficulties. It can be challenging to deliver the gene to the appropriate cells, and introducing a benign viral vector can sometimes stimulate an unwanted immune response from the body. There are also risks associated with integrating the new DNA, as it may interfere with the functioning of another, non-defective gene, leading to potentially life-threatening side-effects. In addition, a number of genetic diseases are caused by several gene mutations acting together, so are very complex to address. Despite this, gene therapy remains an extremely promising approach to treating more than 10,000 human diseases that are the result of a single defective gene.
The personalised approach required for gene therapy offers huge benefits to patients, but the associated costs reflect this, with treatments being much more expensive than conventional medicines. However, the initial financial outlay for treatment may be offset by the savings from reduced hospital visits, prescriptions and other treatments over the lifetime of the patient, as well as immeasurable improvement in the patient’s quality of life. As if often the case, discussions around money seem trite when it comes to curing diseases like blindness, haemophilia, cystic fibrosis and muscular dystrophy, but are an unfortunate necessity in an already resource-pressed healthcare system.
NHS patients were some of the first to benefit from CAR-T therapy, and the UK is – perhaps surprisingly for some – at the forefront of advances in this sector, accounting for 12 per cent of all ongoing advanced therapy medicinal product clinical trials globally.1 Edinburgh Technopole is home to both the Almac Group – which has become the first GMP-accredited lab to produce personalised cancer vaccines for clinical trials – and BioBest, which owns the largest equine stem cell centre in the UK, showcasing the potential for these technologies to benefit other animals.
It’s hard to imagine what people a hundred years ago might have made of these medical advancements that, until recently, inhabited the world of science fiction and the miraculous. Who knows what the future of gene therapy looks like? What we do know is that it is here to stay.