What is a Gene therapy???

A gene is a linear sequence of DNA that codes for a particular protein. On rare occasions, usually during the division of the cell, the nucleotide sequence (the order of the DNA base pairs) of a gene can get jumbled up and mutated, so that the resultant protein is faulty. Such a mutation event is the root cause of genetic diseases such as cystic fibrosis, adenosine deaminase (ADA) deficiency and sickle-cell anaemia. For example, people who suffer from cystic fibrosis produce a faulty cellular transport protein called cystic fibrosis transmembrane conductance regulator, which results in the build-up of mucous in their lungs.

The earliest applications of gene therapy were based on the principle that a disease is caused by a faulty gene (or combination of genes), and if such genes can be replaced with ‘correct’ versions, the disease might be controlled, prevented or cured. Gene therapy is being applied to many different genetic diseases, both congenital (since birth) and acquired. However, most diseases involve multiple genetic factors (they are polygenic). Until the precise involvement of different genes (their regulation and expression) in the disease process and the proteins they encode is established, gene therapy is most likely to be clinically effective as a preventative or curative treatment for single-gene defects such as ADA deficiency, familial hypercholesterolaemia. and cystic fibrosis. Several clinical trials employing gene therapy protocols have already been completed, with some success in patients who have cystic fibrosis and ADA deficiency, although the effectiveness of the protocols was not as dramatic as first envisaged, mainly owing to the inefficiency of the gene transfer vectors that were used.

Originally known as ‘genetic replacement therapy’ during the early 1980s, ‘gene therapy’ has now outgrown its original definition and is applied to all manner of protocols that involve an element of gene transfer, either in vivo or ex vivo, and not necessarily a gene that is known to cause a disease. In vivo gene transfer is the introduction of genes to cells at the site they are found in the body, for example to skin cells on an arm, or to lung epithelial cells following inhalation of the gene transfer vector. Ex vivo gene transfer is the transfer of genes into viable cells that have been temporarily removed from the patient and are then returned following treatment (e.g. bone marrow cells). Gene therapy can be subdivided into somatic cell gene transfer (that is transfer to normal diploid cells), which is the focus of this review, and germline gene transfer (transfer to haploid sperm or egg cells of the reproductive system). The ethical issues associated with germline gene therapy are far more complex than those surrounding somatic cell gene transfer, because the genes are transferred not only to treated individuals but also to their progeny. Germline gene therapy is being widely used for the production of transgenic animals for research, and increasingly for agriculture and biotechnology, but the long-term effects of each transferred gene in animals will need to be carefully monitored and analysed, as well as the significance of any residual vector DNA if applicable. The benefits that the use of germline gene therapy in humans could bring are significant. The development of serious and distressing inherited genetic diseases could be prevented before birth and eliminated in subsequent generations. However, because of the potential for abuse and eugenics, gene therapy in humans needs to be widely discussed and the associated safety issues evaluated before this approach can be used for the treatment of diseases.