Gene Therapy

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PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

In the 1990s there was great hope that this novel approach might provide an answer to many hitherto incurable diseases. The basic idea is to correct defective genes responsible for disease development. This can be achieved in a number of ways:

  • Homologous recombination can be used to swap a defective gene for a normal, functioning one.
  • By altering the regulation of the gene, to effect its function.
  • By using selective reverse mutation to repair a defective gene.
  • The most common method, however, is to insert a normal gene into a nonspecific location to replace a defective gene.

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When a normal gene is inserted into the genome, a carrier molecule (a vector) is used. This will deliver the new gene to the target cells. The most commonly used vectors are viruses. The most commonly used viruses are:

  • Retroviruses
  • Adenoviruses
  • Adeno-associated viruses
  • Herpes simplex viruses

These viruses are altered to carry normal human DNA. The patient's target cells are infected with the vector, which deposits its genetic load including the gene to be replaced. The target cell is then able to produce a functioning protein. More recently, success has been seen by combining a tumour-specific adenovirus vector and several single therapy genes. Targeting gene-virotherapy has killed tumour cells with minimal damage to normal cells in mice.[2][3]

There are also non-viral insertion options.[4] The simplest method is direct introduction of new DNA into the target tissues. This is limited by the type of tissue and the amount of DNA required. An artificial lipid sphere with an aqueous core is created - a liposome - which can both carry the therapeutic DNA and pass it through the target cell's membrane. The therapeutic DNA can also bind chemically to molecules that will attach to target cell receptor sites. These are then taken into the cell's interior. This tends to be less effective than the other methods.

Human gene therapy is still largely in the experimental phase. There have been few big breakthroughs since the first trial started in 1990. There has also been at least one death attributed to therapy and two cases of leukaemia developing post-therapy. There are also technical problems involved:

  • Problems with viral vectors, such as toxicity, inflammatory and immune responses.
  • Disorders resulting from multiple gene defects, such as heart disease, Alzheimer's disease and diabetes, are not good candidates for gene therapy. Single gene defects are the most likely to benefit from gene therapy.
  • Gene therapy tends to be of short duration. The functioning DNA that is introduced must remain functioning and stable to effect a cure. Many cells divide quite rapidly, so multiple treatments may be required.
  • The immune response to any foreign material may reduce the effectiveness of the treatment. It may also make multiple treatments unfeasible.

In a bid to alleviate disease at the earliest possible stage, in utero fetal gene therapy has also been tried.[5] Gene therapy has the potential to have a major role in the management of a range of inherited disorders.[6]

Particular diseases with research showing particular potential benefit from gene therapy include Leber's congenital amaurosis, severe combined immunodeficiency, haemophilia, thalassaemia, Parkinson's disease, age-related macular degeneration, adrenoleukodystrophy, Epstein-Barr virus lymphoma and melanoma.[7] 

Further reading & references

  1. Geisler A, Fechner H; MicroRNA-regulated viral vectors for gene therapy. World J Exp Med. 2016 May 20;6(2):37-54. doi: 10.5493/wjem.v6.i2.37. eCollection 2016 May 20.
  2. Liu XY, Gu JF, Shi WF; Targeting gene-virotherapy for cancer. Acta Biochim Biophys Sin (Shanghai). 2005 Sep;37(9):581-7.
  3. Liu XY, Gu JF; Targeting gene-virotherapy of cancer. Cell Res. 2006 Jan;16(1):25-30.
  4. Li L, He ZY, Wei XW, et al; Recent advances of biomaterials in biotherapy. Regen Biomater. 2016 Jun;3(2):99-105. doi: 10.1093/rb/rbw007. Epub 2016 Mar 5.
  5. Coutelle C, Themis M, Waddington SN, et al; Gene therapy progress and prospects: fetal gene therapy--first proofs of concept--some adverse effects. Gene Ther. 2005 Nov;12(22):1601-7.
  6. Fischer A, Cavazzana-Calvo M; Gene therapy of inherited diseases. Lancet. 2008 Jun 14;371(9629):2044-7.
  7. Frederickson RM; Escaping the valley of death. Mol Ther. 2012 Mar;20(3):476-8. doi: 10.1038/mt.2012.21.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Hayley Willacy
Current Version:
Peer Reviewer:
Dr Adrian Bonsall
Document ID:
2185 (v22)
Last Checked:
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