-mutation in the CFTR gene are associated with the disease state of CF.

, -the treatment of CF is currently directed towards the downstream effects of the disease as yet, there is no clinically avaible theropy designed to correct the effects and cure the CFTR dysfunction.Cystic fibrosis has has amoung the highest number of gene therapy trails; for an inherited disease. With many vector systems being trailed.
-it targets the cause of cystic fibrosis rather than just treating the symptoms of cystic fibrosis.

-History of Cystic Fibrosis Gene Therapy

Subsequent studies have tested other methods of gene delivery, such as: fat capsules, synthetic vectors, nose drops, or drizzling cells down a flexible tube to CFTR cells lining the airways of lungs. Researchers are now testing aerosol delivery using nebulizers.

PROCESS-The defective gene in the case of CF carries the code for a protein called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). This protein normally directs the movement of salt and water in and out of cells. But due to the mutation instead this protein is what causes the thick, mucus typical of CF. To fix this it would be reasonable to state that by replacing this abnormal gene with the normal gene then the protein would then be able to do what it's supposed to do. However we are only in the beginning stages of finding a way to replace and cancel out the defective gene of cystic fibrosis and there are constraints and limitations on what we can do right now. This process is easier said than done as it is still uncertain on how to keep this agent of change to the mutation constant. By identifying one of the defective cells that contain the mutated gene, the vector then unloads its genetic material containing the normal gene into the target cell. The normal gene produces the normal protein which restores the target cell to a normal state. As cystic fibrosis involves more than one cell so the problem isnt fixed. Another consideration is how to get the normal gene to the cell; this is done by a vector, which carries the corrected gene. The first attempt in 1995 used a genetically altered virus adenovirus (They are the usual cause for respitory illness but since they have been altered to be weak they are harmless). After achieving the process of getting the normal gene into the cell researchers are faced with the problem of getting it to go to the right spot on the chromosome. The new gene might alter gene because of changes in the position or chromosomal environment of the gene. this may change the expression or the phenotype of the gene. Although this experiment wasnt successful in regards of curing the disorder it is used as a stepping stone. The use of this vector was an indication that the replacement of the defective gene with a healthy one shows the potential gene therapy has on cystic fibrosis. There is not yet a cure for this inherited disorder as it is still a work in process and is still in an experimental stage. Target cells being the lung cells that are infected with the viral vector. The vector then unloads its genetic material containing the normal gene into the target cell. The normal

gene produces which restores the target cell to a normal state. This protein normally directs the movement of salt and water in and out of cells. But due to the mutation instead this protein is what causes the thick, mucus typical of CF.

scientists remain positive about gene therapy. There are 2 main areas that need be improved in the future for better results:

A more guaranteed method of infusing the healthy gene into the affected cells. Finding a way to make the cure permanent.

One of the first limitations is how to get the 'normal' gene to replace the one. Replacing the defective gene in one cell wouldn't be good enough since there is more than one cell involved in the disease. Once the corrected gene was inserted into the cell, the next problem is getting it to go to the right place. Each cell in the human body contains 22 pairs of autosomal chromosomes, or chromosomes that are not associated with sex chromosomes. Remember that the gene for CF is found only on chromosome 7. To do this, gene delivery vehicles called vectors, , are used. The first vector used was an attenuated or weakened adenovirus. Adenoviruses are responsible for a number of respiratory illnesses but since they are weakened they are harmless to use for gene therapy. The use of this virus was the first evidence that it's possible to get the healthy gene for CF into the lungs (Fackelmann, 1994).
the healthy gene will insert itself randomly in the cell DNA. The new gene might alter the phenotype, or the expression, of the gene because of changes in the position or chromosomal environment of the gene. This is called position effect (McClean, 1997). Depending on where the new gene inserts, since it is a random insertion, it can be harmful or helpful. Before gene therapy can be used to treat CF patients, researchers must find a better way to deposit these healthy genes into the body. The first gene therapy experiments involve lung cells because they are readily accessible and lung damage is the most life-threatening problem. Researchers know that the gene can be safely transferred into CF airways of the lungs and will express itself. They now need to take information from experiments and refine the delivery methods to carry healthy genes to damaged cells in other organs affected by CF (Cystic Fibrosis Foundation, 1998).

But finding the best delivery system for transporting normal CFTR genes is only one problem that scientists must solve to develop an effective treatment for CF. Scientists must also determine the life span of affected lung cells, identify the "parent cells" that produce CFTR cells, find out how long treatment should last and how often it needs to be repeated.

the Cystic Fibrosis Transmembrane Regulator (CFTR) gene - causes CF. The gene was discovered in 1989. Since then, more than 900 mutations of this single gene have been identified. What is

gene therapy other ways -The most common form of a gene therapy involves inserting a normal gene to replace an abnormal gene. -Replacing a mutated gene that causes disease with a healthy copy of the gene. -inactive or turning off a muted gene that is functioning abnormally. not carried on the sex chromosomes and males and females are both afflicted by this disease. Recessive inheritance is when both parents "carry" the abnormal gene in their DNA but they themselves do not show evidence of the disease. The mother and father have one normal gene and one abnormal gene and don't show signs of disease because the normal gene dominates the abnormal gene. To have CF, a child must inherit two abnormal genes, one from each parent. Remember that chromosomes are made up of DNA or deoxyribonucleic acid. DNA is made up of genes, and genes are made up of building blocks called base pairs. The specific gene responsible for CF was identified in 1989 on human chromosome 7 (Pseudomonas Genome Project, 1998). A mutation, or change in the genetic material, resulting in a substitution or loss of one of the base pairs causes the CF gene to be abnormal (Cystic Fibrosis Foundation, 1995). The basic problem for all patients however is an abnormality in glands, which produce mucus or sweat. The mucus produced by people with CF is thick and sticky instead of thin and watery. The major systems most affected by CF are the respiratory and the digestive. In the digestive system, mucus can block the supply of enzymes used to break down food. The result of the blockage of such enzymes is malnutrition. The patient will have an excessive appetite but will not experience any weight gain