‘The PastThe Birth of Gene Therapy’


The concept of gene therapy was first put forward in the 1960s and early 1970s- a period of time where Watson, Crick, Franklin and Wilkins shed light on the structure of DNA and Avery, MacLeod and McCarty showed DNA was responsible for imparting traits upon an organism.

In 1970 Stanfield Rogers proposed the use of “good” DNA to replace “defective” DNA as a treatment for inherited diseases. The concept quickly captured the imaginations of scientists, patients and the public alike with its promise to cure genetic diseases such as haemophilia, β-thalassemia and sickle cell anaemia. The race was on to turn this concept into a reality.


The trials begin


The first gene therapy clinical trial was approved in 1990. Two patients with ADA-SCID -an inherited disease that prevents the normal development of the immune system- were treated with a virus carrier modified to carry the ADA gene into cells, whilst harmful elements of the virus were removed to make it safe. This protocol combined both gene and cell therapies as immune cells were taken from the patient, corrected using gene therapy and then returned to the patients. In both patients the immune system was strengthened, but the effect was transient. 

Numerous other trials followed, but despite early promise, by the end of the decade no gene therapy trial showed long-term improvements in patients, leading the field to go back to the drawing board. Clinical trials were redesigned, new models of disease developed and vectors improved upon after years of research.


gene model


‘The Present – The era for progress’


The current era for genetic medicines has been hallmarked by unparalleled successes in patients. As a result huge sums are being invested in developing and commercialising genetic and cell based medicines, and a large number of biotechnology companies have been spun-out from universities around the world.

In 2012 a gene therapy medicine developed to treat a rare disease, familial lipoprotein lipase deficiency (LPLD), became the first to be approved for sale in Europe. The medicine is injected into the leg muscles of patients with familial LPLD and consists of the human LPL gene carried into the cells by an adeno-associated virus (AAV) vector.

LPLD is a rare genetic disorder that can cause severe inflammation of the pancreas resulting from an inability of the body to break down fatty acids due to mutations in the LPL gene. A recent study followed up treated patients and found that even 5 years after one dose, the treatment remained effective. This suggests that a single injection into muscles may be sufficient to provide a long-lasting and potentially life-long therapy.


Out of the bubble and into the market


Perhaps the most regularly cited success story has been in the treatment of severe combined immunodeficiency’s (SCID) - sometimes called bubble boy disease- where the immune system does not develop properly leaving patients susceptible to dying from even minor infections. Scientists around the world have demonstrated that SCID patients can now effectively be “cured” with a single dose of gene therapy. Importantly, and in contrast to the early ADA-SCID studies described above, the treatment is now long lasting and continues to work over 10 years after treatment. This work has been led by a number of scientists worldwide and in 2016 the European Medicines Agency approved the sale of this medicine in Europe for the treatment of ADA-SCID.

A number of pharmaceutical and biotech companies are now expected to apply for market approval in the US and Europe following their own successful clinical trials. This includes a gene therapy for blindness caused by mutations in the RPE65 gene. Here, an AAV vector carrying the correct version of the RPE65 gene is injected into the retina, improving sight.


Genetic medicines for all


Moving on from the ultra-rare diseases described above, AAV carrying the factor 9 gene into liver cells is being investigated for haemophilia B and a number of treated patients have been able to stop taking infusions of factor 9 protein, the standard treatment for haemophilia B.  

The technologies and techniques used to cure some forms of SCID with gene therapy are now being used for other diseases including β-thalassemia, where the β-globin gene is delivered to haematopoietic stem cells outside of the body and the corrected cells returned. A similar approach is being used to target cancers by introducing genes that re-target immune cells and enable them to both identify and kill cancer cells.

Viruses have also been modified to replicate only in cancer cells causing them to rupture and die. The viruses also carry genes to produce proteins that activate the immune system. This two-pronged attack has been extremely effective in shrinking tumours in patients with late stage melanoma.


layal cancer


‘The Future – Unbound possibilities’


The examples cited above represent the tip of the iceberg, clinically. Undoubtedly the future of genetic medicines is very bright with scientists and investors alike bullish about their prospects. This is highlighted by the startling statistic that gene and cell therapy companies have been able to raise in excess of $10 billion in 2015 alone. This is despite that, at the time of writing, only two gene therapy drugs have been licensed for sale in Europe.

Unlike the early years of gene and cell therapy, today the hype is based not only on the theoretical potential for gene and cell therapies, but on real and long-lasting improvements seen in patients. The glut of positive data keeps coming in and is usually presented first at gene and cell therapy conferences including the British Society for Gene and Cell Therapy (BSGCT) annual meeting, with the next one being held at the Royal Welsh College of Music and Drama, Cardiff.

In addition to the latest clinical and pre-clinical data being presented, delegates and invited speakers will be debating the future challenges for genetic medicines including regulation of gene and cell therapies, ethical issues related to genome editing and the advances and investment needed to enable scaling up of these medicines so that enough can be produced to meet the needs of patients.

BSGCT runs a public engagement day every year where those interested can ask questions and learn more about gene and cell therapy research from those conducting the research. The next PED event will be held at the Oxford University Museum of Natural History.

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It is clear now that the long ago promised gene therapy treatments are beginning to materialise and the era of personalised genetic medicines is well and truly here and here to stay.

BSGCT runs a public engagement day every year where those interested can ask questions and learn more about gene and cell therapy research from those conducting the research. The next PED event will be held at the Oxford University Museum of Natural History.

To read more on the latest advances in gene and cell therapy visit BSGCT Blogs and follow BSGCT on;