Gene Therapy
Genes are the basic physical and functional units of heredity. Genes control heredity and provide the basic biological code for determining a cell's specific functions. Gene therapy is a rapidly growing field of medicine in which defective genes responsible for disease development are corrected during the treatment. The technology is still in its infancy.
The Food and Drug Administration (FDA) has not yet approved any human gene therapy product for sale. Current gene therapy is experimental and has not proven very successful in clinical trials. Little progress has been made since the first gene therapy clinical trial began in 1990. In 1999, gene therapy suffered a major setback with the death of 18-year-old Jesse Gelsinger. Jesse was participating in a gene therapy trial for ornithine transcarboxylase deficiency (OTCD). He died from multiple organ failures 4 days after starting the treatment. His death is believed to have been triggered by a severe immune response to the adenovirus carrier.
One of the following approaches may be used for correcting faulty genes:
- A normal gene is inserted into a nonspecific location within the genome to replace a nonfunctional gene. This is the most common approach.
- An abnormal gene is swapped for a normal gene through homologous recombination.
- The abnormal gene is repaired through selective reverse mutation in order to return it to its normal function.
- The regulation (the degree to which a gene is turned on or off) of a particular gene is altered.
How does gene therapy work?
A normal gene is inserted into the genome to replace an abnormal (disease-causing) gene. A carrier molecule called a vector is used to deliver the therapeutic gene to the patient's target cells. The most common vector used now-a-days is a virus that has been genetically altered to carry normal human DNA.Target cells (-for mesothelioma, lung cells-) are infected with the viral vector. The vector 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.
There are several nonviral gene-delivery systems as well. Direct introduction of therapeutic DNA into target cells is the simplest method. This approach is limited in its application because it can be used only with certain tissues and requires large amounts of DNA.
In another nonviral approach, the creation of an artificial lipid sphere with an aqueous core. This liposome carries the therapeutic DNA and is capable of passing the DNA through the target cell's membrane.
Therapeutic DNA also can get inside target cells by chemically linking the DNA to a molecule that will bind to special cell receptors. Once bound to these receptors, the therapeutic DNA constructs are engulfed by the cell membrane and passed into the interior of the target cell. This delivery system tends to be less effective than other options.
Researchers also are experimenting with introducing a 47th (artificial human) chromosome into target cells. This chromosome would exist autonomously alongside the standard 46 --not affecting their workings or causing any mutations. It would be a large vector capable of carrying substantial amounts of genetic code, and scientists anticipate that, because of its construction and autonomy, the body's immune systems would not attack it. A problem with this potential method is the difficulty in delivering such a large molecule to the nucleus of a target cell.
Disadvantages of Gene Therapy
- Short-lived nature of gene therapy
- Immune response
- Problems with viral vectors (once inside the patient, viral vector may recover its ability to cause disease).
- Multigene disorders