Functional cystic fibrosis transmembrane regulatory channel proteins are produced and incorporated into the cell membranes,alowing chloride ions to leave the cell thus preventing the thick sticky mucus asociated with the symptoms of cystic fibrosis. The treatment is only temporary because the epithelial cells in the airways die and the new cells in their place do not contain the normal allele. The longest correction in the trials has lasted for about two week 2 weeks, so patients would have to be treated regularly throughout their lives.
An alternative method uses a virus called adeno-associated virus (AAV). The AAV does not normally cause any human diseases, so can safely be used to help put back the normal CFTR allele. Cells actually become "infected" with normal CFTR. This is done by first taking out the normal virus genes, which allow it to reproduce or make additional infectious copies of itself. The normal CFTR gene is then inserted into the virus. The new virus is called an adeno-associated virus mediated CFTR vector (AAV-CFTR). This virus can then enter CF human cells and instruct them to make normal CFTR proteins. Since AAV-CFTR does not contain the main virus genes, it is unlikely to produce an immune response and is also more long term than using liposomes.
Public debate over the ethics of using gene technology to treat human beings raged long before the technology became available for gene therapy. The prospect of altering genes brings forward questions about "playing God." One of the early concerns was that genetic material used to treat somatic cells would find its way into sperm and ova, thus affecting offspring of the patient. By careful selection and targeting cells, however, spread of genetic material to germ cells has not occurred. Gene therapy has not yet had the success anticipated by many scientists: effectiveness of treatment for most diseases has been disappointing, though it has been encouraging for some.
Many people think that somatic cell therapy will lead to altering germ cells (gametes) so that every cell in the body contains the new allele. Germ-line therapy is much more technically difficult. Any experiments in this would involve great uncertainty and clinical risk. Also the long-term effects of this are unknown and patients would have to be followed for decades. Germ-line therapy is carried out in gametes. The identification of a defective gamete involves in vitro fertilization (IVF).
For IVF, a woman is given hormones to stimulate her ovaries to produce many mature eggs at once. The eggs are obtained by two different manners: the first, guided by ultrasound, the surgeon passes a needle through the vagina into the follicles removing the eggs by aspiration (suction). This is called ultra-sound guided aspiration with intravenous analgesia. The other method is by laparoscopy with general anaesthesia. In this technique, the specialist guides the needle through the abdominal wall into the ovarian follicle looking through the laparoscope. The eggs are then placed in a special dish and fertilized with her partner’s sperm before being implanted into the woman’s uterus. During the three-day period when mature eggs are fertilized and before they are implanted into the uterus, one or two cells are extracted from each embryo for genetic testing.
This is significant because if IVF is used to identify a potential disease in a gamete, then one can avoid the disease by simply discarding that gamete. Those who consider it wrong to destroy a pre-embryo have a stronger reason to pursue gene therapy, however, these same people would probably also criticize researching on embryos to perfect the techniques of the therapy, and object to the IVF procedure, so would be unlikely to use gene therapy anyway. This raises the question of why research in germ-line gene therapy should be pursued at all.
It is believed that it would open the doors for attempts to alter human traits not associated with disease such as altering the gene pool for good by the enhancement or modification of human capabilities, thus increasing the standards of a normal human being. For example, some extremists believe that superior humans will be produced who will reduce normal humans to menial servitude.
These things would be most easily available to the rich as gene therapy is expensive, so would increase the problems of class distinctions. Also it would be only those in developed countries that could afford it, so the gap between the developed and the developing would become even greater.
Another concern is that the important functions may accidentally or unknowingly be altered, which could lead to a decrease in species fitness. Also, germ-line modification may effect evolution and threaten future generations as well.
