One of the most amazing genetic applications in medicine is gene therapy. Also known as somatic gene therapy, this procedure involves inserting (or sometimes deleting) portions of the genes in diseased patients so that they can be cured and live healthier lives.
Gene therapy changes the expression of some genes in an attempt to treat, cure, or ultimately prevent disease. Current gene therapy is primarily experiment based, with a few early human clinical trials under way. Theoretically, gene therapy can be targeted to somatic (body) or germ (egg and sperm) cells.
• In somatic gene therapy the recipient’s genome is changed, but the change is not passed along to next generation.
• This form of gene therapy is contrasted with germ line gene therapy, in which a goal is to pass the change on to offspring. Germ line gene therapy is not being actively investigated, at least in larger animals and humans, although a lot of discussion is being conducted about its value and desirability.
Gene therapy should not be confused with cloning, which has been in the news so much in the past year. Cloning, which is creating another individual with essentially the same genetic makeup, is very different from gene therapy.
Genes, which are carried on chromosomes, are the basic physical and functional units of heredity. Genes are specific sequences of bases that encode instructions on how to make proteins. Although genes get a lot of attention, it’s the proteins that perform most life functions and even make up the majority of cellular structures. When genes are altered so that the encoded proteins are unable to carry out their normal functions, genetic disorders can result.
Gene therapy is a technique for correcting defective genes responsible for disease development. Researchers may use one of several approaches for correcting faulty genes:
• A normal gene may be inserted into a nonspecific location within the genome to replace a nonfunctional gene. This approach is most common.
• An abnormal gene could be swapped for a normal gene through homologous recombination.
• The abnormal gene could be repaired through selective reverse mutation, which returns the gene to its normal function.
• The regulation (the degree to which a gene is turned on or off) of a particular gene could be altered.
Each of us carries about half a dozen defective genes. We remain blissfully unaware of this fact unless we, or one of our close relatives, are amongst the many millions who suffer from a genetic disease.
About one in ten people has, or will develop at some later stage, an inherited genetic disorder, and approximately 2,800 specific conditions are known to be caused by defects (mutations) in just one of the patient’s genes.
Some single gene disorders are quite common—cystic fibrosis is found in one out of every 2,500 babies born in the Western World—and in total, diseases that can be traced to single gene defects account for about 5 per cent of all admissions to children’s hospitals.
How Does Gene Therapy Work?
In most gene therapy studies, a “normal” gene is inserted into the genome to replace an “abnormal,” disease causing gene. A carrier molecule called a vector must be used to deliver the therapeutic gene to the patient’s target cells. Currently, the most common vector is a virus that has been genetically altered to carry normal human DNA.
Viruses have evolved a way of encapsulating and delivering their genes to human cells in a pathogenic manner. Scientists have tried to take advantage of this capability and manipulate the virus genome to remove disease-causing genes and insert therapeutic genes.
• Target cells such as the patient’s liver or lung cells are infected with the viral vector. The vector then unloads its genetic material containing the therapeutic human gene into the target cell. The generation of a functional protein product from the therapeutic gene restores the target cell to a normal state.
• In gene therapy trials, scientist have used a variety of different ways to deliver the genes for VEGF-1, VEGF-2 and FGF 4 into the hearts of patients with advanced myocardial ischaemia, after gene therapy, patients had less severe angina (chest pain) and their hearts worked better.
Similarly, after gene delivery of VEGF to patients with limb ischaemia, the blood supply improved and leg sores healed better. Gene therapy has prevented below-knee amputation in some patients for whom amputation had been recommended.
• Gene therapy has also been successful in preventing re-occlusion, or re-blockage, of coronary artery bypass grafts and in keeping arteries open after angioplasty surgery.