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The Outlook for Gene Therapy

Gene Therapy Posted on: 26 Aug 03


As it aims to correct the underlying genetic defects in human disease rather than just focusing on symptoms, gene therapy offers the potential for actual cures. However, several technical and safety issues have hampered progress.

Gene therapy is considered to be one of the most exciting areas of medicine for the future. As it aims to correct the underlying genetic defects in human disease rather than just focusing on symptoms there is the potential for an actual cure. Following the completion of the draft of the human genome, there was considerable media attention on gene therapy, but various safety concerns and technical problems have shown that many hurdles remain.

A promising start

In general, the US has been at the forefront of efforts to develop this form of disease treatment. In 1990, the first successful human gene therapy was carried out at the National Institutes of Health (NIH) (1). A young patient was treated for adenosine deaminase (ADA) deficiency, a genetic condition that results in a immune deficiency disorder called severe combined immunodeficiency disease, which leaves patients prone to repeated serious infections.

Unfortunately, only slow progress was made over the next ten years, even though more than 400 clinical trials to test gene therapy for a range of different diseases were launched around the world (2).

Technical and safety problems

A large part of the problem has been in determining how to deliver sufficient quantities of therapeutic genes in a safe manner. As systemic and biological barriers tend to interfere with the delivery of therapeutic genes, researchers have had to employ transfection vectors in order to deliver the genetic material into cells (3).

At present, the transfection vectors employed involve viral and non-viral mechanisms. Viral transfection vectors are considered more efficient than non-viral options, but because of their origins there are serious immunogenic concerns associated with their use (3). Although non-viral methods have been developed, such as liposomes, ‘targetibility’ still remains a problem. For example, non-specific electrostatic interactions with cellular components can interfere with the delivery of therapeutic genes by these systems (3).


In 1999, the safety concerns over the manner in which gene therapy trials were being carried out were highlighted by the death of an 18-year old participant in a US trial (4). The U.S. Food and Drug Administration (FDA) acted swiftly and suspended all gene therapy clinical trials at the centre (5). The authorities recommended numerous changes in order to increase the safety of using adenovirus vectors (4). This situation also shifted the emphasis of many gene therapy researchers to non-viral vectors.

 Another setback for gene therapy occurred in 2002 when it was reported that a child being treated in France for x-Severe Combined Immunodeficiency syndrome (x-SCID) showed signs of having developed leukaemia after undergoing treatment (7). This was extremely disappointing as initial work by the French group had been promising and earlier that year, a child in the UK had successfully been treated for the same condition using gene therapy (7, 8).

Pending further discussions, the authorities in France decided to halt the trials in this area as did officials in the US, where three similar trials were being carried out (7). Interestingly, advisors to the UK government decided against halting similar trials although they promised to closely monitor treatments (7).

Stricter regulation

The continuing worry over safety issues has led to a welcome tightening of the regulations surrounding gene therapy trials around the world.

In the US, gene therapy trials are regulated by the NIH and the FDA. The NIH has a special committee, the Recombinant DNA Advisory Committee (RAC), which focuses on this area of research (1). No trial can progress without full approval and sign off from these authorities. The FDA has made a considerable effort to reassure the public and healthcare professionals over safety concerns. For example, in March 2000, it launched random inspections of 70 clinical trials in more than two dozen gene therapy programs (2).

In the UK, the need for tight regulations has long been recognised and is managed through the Gene Therapy Advisory Committee (GTAC). In 1999, when the first death during a gene therapy trial occurred in the US, the GTAC had already been involved in a review of the serious adverse events and issues related to the monitoring of patients involved in gene therapy research (9). In 2000, more than 50% of European gene therapy clinical trials were taking place in the UK (10).

Germany also re-examined its regulations but theauthorities decided to allow certain trials involving retroviral vectors to continue. Specifically, an AIDS gene therapy trial was allowed to go ahead in 2003, but under close supervision (11).

Cautious optimism

The recent setbacks in gene therapy have tended to dampen down media coverage of work in this area. Yet it is worth pointing out that although the rate might be slower than initially expected progress is being made. Furthermore, better regulation of this area of research will increase the confidence of the public.

As the UK’s GTAC highlights in its recent Ninth annual report,  “the success achieved by the French Group in treating infants with X-SCID with gene therapy must not be overlooked. However, such trials must proceed with caution. Only by doing so can we ensure that gene therapy can make the difficult transition from being a laboratory experiment to being a clinical reality” (12).


  1. Gene Therapy Basics. American Society of Gene Therapy.
  2. Thompson L. (2000). Human Gene Therapy Harsh Lessons, High Hopes. FDA Consumer magazine September-October 2000.
  3. Chaudhuri A. (2003). Cationic Liposomes - Promising gene carriers in non-viral gene therapy.
  4. Hollon T. (2000). Researchers and regulators reflect on first gene therapy death. Nature Medicine. Volume 6 Number 1 p 6.
  5. FDA suspends trials at gene-therapy lab. January 22, 2000.
  6. Institute for Human Gene Therapy's Response to FDA.
  7. Gene therapy trials halted. BBC News. 3 October, 2002.
  8. The first successful human gene therapy trial: Correction of an immune deficiency. Institut National de la Santé et de la Recherche Médicale (INSERM). April 27th, 2000 Press Release.
  9. Sixth Annual Report (2000). Gene Therapy Advisory Committee. Health Departments of the United Kingdom.
  10. Seventh Annual Report (2000). Gene Therapy Advisory Committee. Health Departments of the United Kingdom.
  11. Commission of Somatic Gene Therapy decides Continuation of Some of the Gene Therapy Studies with Retroviral Vectors. Joint Press Release of the Paul-Ehrlich-Institut and the German Medical Association. February 2003.
  12. Ninth Annual Report (2002). Gene Therapy Advisory Committee. Health Departments of the United Kingdom.

Dr Faiz Kermani

Last updated on: 27/08/2010 11:40:18

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