Gene Therapy

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Gene Therapy

Gene therapy is the process of manipulating genetic material either to treat a disease or to change a physical characteristic. It is accomplished by introducing a normal gene into the cell to make up for a defective or missing gene. Although some successes have been achieved, this technique is still in the research stage.

Once the scientific knowledge about genes and genetics had reached a certain level of sophistication by the early 1970s, scientists started thinking seriously about going right to the source of certain conditions and diseases and replacing bad genes with good genes. That is how gene therapy might be described in a simple way. Instead of introducing a therapeutic product like a drug into the body, scientists would try to deliver a gene to cure the problem once and for all.

In theory, the notion of gene therapy seems very attractive. It would allow new genetic material to be inserted into the cells in a patient's body to correct or improve a particular cell function; to make diseased cells even more vulnerable to being destroyed; or to block the functioning of diseased cells altogether. Again in theory, the way this is accomplished sounds feasible. If an individual has a disease that is the result of inheriting

two copies of a defective gene, he or she would be a candidate for gene therapy. First, a new and properly functioning gene would be isolated from normal cells. Called the "transfer gene," this gene would be removed by cutting deoxyribonucleic acid (DNA) at specific locations using a technique called "gene splicing." Then a genetically altered virus would be used as the vehicle (called a "vector") to deliver the new gene to the cells. In fact, this has already been accomplished, and the first successful gene therapy experiment was performed in 1990. In that case, doctors replaced the defective genes of a four-year-old girl whose immune system did not work. Her body would not produce the necessary enzyme named adenosine deaminase (ADA). Doctors inserted a normal ADA gene into immune cells taken from her body and then returned the treated cells to her with a blood transfusion. The new gene gave the cell instructions to produce the enzyme and her immune system began to recover.

STILL NEEDS TO BE PERFECTED

Despite this success, researchers have discovered that the major limitation of gene therapy is the delivery system. They must always use a safe, efficient vector, or vehicle, to carry the new DNA to targeted cells. The early use of viruses as vectors was a logical strategy since viruses have been easily invading people's cells and causing trouble for thousands of years. Once there, viruses inject their own genes into the human cells, and the viral cells instruct them to make more viruses. Biologists have tried to turn the tables on viruses, and they carefully treat viral DNA in the laboratory so that it cannot reproduce itself once it gets into the body. Then human genes are inserted into the treated viral DNA, and this modified viral DNA is then introduced into human cells. Because it is carried by a virus, the modified DNA quickly finds its way into the DNA of the cells and becomes active. In practice, however, viruses infect cells in an unpredictable manner and can sometimes cause unwanted results. For example, inserting viral DNA into a cell might accidentally trigger the cell's oncogenes—specialized genes that can activate an uncontrolled cellular growth of cancer. In 1993 gene therapy for cystic fibrosis had to be stopped when the patient developed lung inflammation. In 1999 a young male patient actually died from a gene therapy treatment that went wrong. In the fall of that year, eighteen-year-old Jesse Gelsinger of Arizona died after undergoing experimental genetic therapy a the University of Pennsylvania. The young man suffered from an inherited liver disorder and was given new genes as an attempt to cure him. While it is not yet known if mistakes were made in his treatment and therapy, his tragic loss underscores the dangers or conducting experiments on humans.

One alternative to the use of viruses in gene therapy is the technique of packaging genes into fatty globules. This has been used to fight tumors that often grow when the immune system fails to recognize the tumor cells as foreign and does not kill them. By wrapping the new gene in droplets of fat, called liposomes, which bind easily to cell surfaces, scientists have been able to experimentally insert a gene that marks the tumor cells in a way that forces the immune system to attack them. Researchers are working steadily at trying to make their methods of transferring genes into human cells more effective, efficient, and safe.

Although gene therapy is still in its early stages, researchers are confident that it will become a standard, accepted strategy for fighting diseases like cancer in the future. Contrary to what many people believe, however, gene therapy is different from genetic engineering since it does not target sex cells that pass along genetic traits. Rather, gene therapy attempts to fix existing problems in ordinary cells and does not tamper with genes in eggs or sperm. Thus, a person who has a single-gene disorder corrected by gene therapy can still pass on a faulty copy of a gene to his or her children. Unlike gene therapy, the more ambitious and fundamentally different goal of genetic engineering is preventative. Genetic engineering seeks to keep diseases from happening in the first place. This process is more controversial since it involves changing genes in the sex cells and gives rise to many ethical and legal issues.