In the 1990s there was great hope that this novel approach may 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:

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:

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.[1][2] There are also nonviral insertion options. 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 cells 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:

In a bid to alleviate disease at the earliest possible stage, in utero fetal gene therapy has also been tried.[6] Prenatal screening for severe genetic disease such as Crigler-Najjar syndrome, Pompe's disease and haemophilia B has been tested in mouse models. There have been issues with the development of liver tumours, insufficient target cells are reached and the therapy is not toxic enough to target cells. There are attempts underway to manufacture antitumour vaccines.In this technique Epstein-Barr virus vectors mediate gene transfer into human B lymphocytes.[7] Other areas of research include:

A recent trial, approved by the American Food and Drug Administration, is for the treatment of Parkinson's disease. This is a phase 1 clinical trial with 11 patients already enrolled. They are aiming to produce the neuroprotective and restorative subthalamic glutamic decarboxylase. There have been no adverse events reported to date.[13]

Read more here:
Gene Therapy | Doctor | Patient.co.uk

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