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 Subject
Index Alphabetical Index
News Basic
Information
About
the Project Medicine
& Ethical,
Legal, Education Research
Publications
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Quick Links to this page
Gene therapy is a novel approach to treat, cure, or ultimately prevent disease by changing the expression of a person's genes. Gene therapy is in its infancy, and current gene therapy is primarily experimental, with most human clinical trials only in the research stages. 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 the next generation. In germline gene therapy, the parent's egg or sperm cells are changed with the goal of passing on the changes to their offspring. Germline 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. Many people falsely assume that germline gene therapy already is being done with regularity. News reports of parents selecting a genetically tested egg for implantation or choosing the sex of their unborn child may lead the public to think that gene therapy is occuring. Actually, in these cases, genetic information is being used for selection. No cells are altered or changed. For more on germline engineering, see Website. Note: "Inadvertent" Germline Gene Transfer Gene therapy is very young and experimental. Many factors have prevented researchers from developing successful gene therapy techniques. The first hurdle is the gene delivery tool. How is a new gene inserted into the body? This is done via vehicles called vectors (gene carriers), which deliver therapeutic genes to the patients' cells. Currently, the most common vectors are viruses. 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 the virus's biology and manipulate its genome to remove the disease-causing genes and insert therapeutic genes. Viruses, while effective, introduce other problems to the body --toxicity, immune and inflammatory responses, and gene control and targeting issues. Some alternatives to viruses that have been considered are complexes of DNA with lipids and proteins. Researchers are also experimenting with introducing a 47th (artificial human) chromosome to the body. It would exist autonomously along side the standard 46 chromosomes --not affecting their workings or causing any mutations. It would be a large vector capable of carrying substantial amounts of genetic code, and it is anticipated that, because of its construction and antonomy, the body's immune systems would not attack it --producing the negative responses described for viruses in the previous paragraph. See also Scientists Try to Build a Better Chromosome.
Another hurdle is understanding gene function. Of the estimated 100,000 genes, scientists know the function of a very few. Attempting gene therapy without knowing how everything works could address only some of the genes implicated in particular diseases. Likewise, genes may have more than one function. For example, consider Sickle Cell Anemia. Sickle cell anemia is caused by an error in the gene that tells the body how to make hemoglobin. Sickle cell anemia is prevalent among African Americans. Children who inherit two copies (one from each of their parents) of the gene for Sickle Cell Anemia will have the disease. Children who inherit only one copy will not. The error in the hemoglobin gene results from a genetic mutation that occurred many thousands of years ago in people in parts of Africa, the Mediterranean basin, the Middle East, and India. A deadly form of malaria was very common at that time, and malaria epidemics caused the death of great numbers of people. Studies show that in areas where malaria was a problem, children who inherited one sickle hemoglobin gene--and who, therefore, carried the sickle cell trait--had a survival advantage: unlike the children who had normal hemoglobin genes, they survived the malaria epidemics; they grew up, had their own children, and passed on the gene for sickle hemoglobin. Once the human genome sequence is complete, the next step in genome research will be functional genomics --understanding what the function of each gene is. For more on functional genomics, see http://www.ornl.gov/hgmis/faq/compgen.html. A third hurdle is multigene disorders. Most genetic disorders involve more than one gene. In only a handful of genetic diseases, like Huntington's Disease, does inheriting one particular gene mean that you have a 100% chance of developing the disorder. Most diseases involve the interaction of several genes and the environment. Many people who develop cancer not only inherit the disease gene for their disorder, they may also have not inherited particular tumor suppressor genes. Diet, exercise, smoking, and other environmental factors may have contributed to their disease. Studies of identical twins show that individuals with the same genetic makeup do not develop the same diseases and disorders. This is irrefutable evidence of the role environment plays in gene expression. High costs associated with developing this novel technology, and regulations associated with human experimentation are also hurdles for researchers in this field. Ethical Issues in Gene Therapy --Some Questions to Consider... What is normal and what is a disability or disorder, and who decides? Are disabilities diseases? Do they need to be cured or prevented? Does searching for a cure demean the lives of individuals presently affected by disabilities? Is somatic gene therapy (which is done in the adult cells of persons known to have the disease) more or less ethical than germline gene therapy (which is done in egg and sperm cells and prevents the trait from being passed on to further generations)? In cases of somatic gene therapy, the procedure may have to be repeated in future generations. Preliminary attempts at gene therapy are exorbitantly expensive. Who will have access to these therapies? Who will pay for their use?
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