Christine Kusznir



GENE THERAPYCystic Fibrosis CFPeople with CF may have the following symptoms:?persistent cough, particularly with physical effort some difficulty in breathing or wheezing with effort tiredness, lethargy or an impaired exercise ability frequent visits to the toilet salt loss in hot weather which may produce weakness poor appetiteCystic fibrosis is an inherited disease of the mucus glands. It causes chronic, progressive damage to the respiratory system, chronic digestive system problems, and can affect other organs. Mucus is a slippery substance that lubricates and protects the lining of the airways, digestive system, reproductive system, and other organs and tissues.The signs and symptoms of this disorder are caused by the production of abnormally thick, sticky mucus in the body's organs. Specific cells in these organs normally produce mucus and other watery secretions. In cystic fibrosis, these cells produce secretions that are thicker than normal, causing disruptions in the body's water balance and ability to handle salt. Problems with breathing are among the most serious symptoms. Mucus can obstruct the airways and cause bacterial infections in the lungs, leading to chronic coughing, wheezing, and inflammation. Over time, mucus buildup and infections lead to permanent lung damage, including the formation of scar tissue (fibrosis) and cysts in the lungs.What Causes Cystic Fibrosis?A defect in the CFTR gene causes cystic fibrosis (CF). This gene makes a protein that controls the movement of salt and water in and out of your body's cells. In people who have CF, the gene makes a protein that doesn't work right. This causes thick, sticky mucus and very salty sweat.The function of the Normal CFTR gene This protein functions as a channel across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. The channel transports negatively charged particles called chloride ions into and out of cells. The transport of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus. The CFTR protein is a channel protein that controls the flow of H2O and Cl? ions in and out of cells inside the lungs.CF is characterized by the buildup of thick mucus in the lungs.1. CFTR protein is working correctly Ions freely flow in and out of the cells2. CFTR protein is malfunctioning Ions cannot flow out of the cell due to a blocked channelBecause there is too little salt and water on the outside of the cells, the thin layer of mucus that helps keep the lungs free of bacteria becomes very thick and difficult to expel by coughing. This thick mucus can clog the airways and lead to dangerous infections. Although advances in the understanding and treatment of the condition have allowed many people with the disease to live into their early 40s, the majority of patients with cystic fibrosis die of respiratory failure. How Is Cystic Fibrosis Inherited?CF is ‘autosomal recessive’ meaning that it occurs equally in males and females.The CF gene must be inherited from both parents and it can ‘skip’ generations.In Australia, one in 2,500 babies are born with CF - that’s one every four days. On average one in 25 people carry the CF gene - most of whom are unaware that they are carriers. Because carriers of CF are unaffected (and therefore show no symptoms) it is hard for them to appreciate that CF may be a real risk. Any of us could be a carrier and we wouldn’t know – think about it, that’s about 1 million unaware carriers – it could be you!Every person inherits two CFTR genes—one from each parent. Children who inherit a faulty CFTR gene from each parent will have CF. Children who inherit a faulty CFTR gene from one parent and a normal CFTR gene from the other parent will be "CF carriers." CF carriers usually have no symptoms of CF and live normal lives. However, carriers can pass the faulty CFTR gene on to their children. Example of an Inheritance Pattern for Cystic FibrosisLet R = Normal alleler = Cystic Fibrosis alleleGene therapy treatment For Cystic fibrosis sufferers in the worksFebruary 16, 2009 by admin? found that a laboratory-created “super” virus could be used to deliver a healthy version of a gene into cells affected by cystic fibrosis, ridding them of the disease.The discovery is the latest boost for a technique called gene therapy, which scientists hope can attack genetic diseases.Previous studies have shown that scientists can “turn off” the faulty gene which causes cystic fibrosis by replacing it with a healthy copy.However, the effects have proved fleeting because the viruses used to carry the “good” gene into cells are quickly attacked by the body’s immune system.Now scientists have been able to create a much stronger virus, with no side effects, capable of resisting the body’s defences.Viruses are one of two key ways that scientists hope they can carry healthy genes into sufferer’s cells.The scientists genetically modified a harmless virus, known as adenovirus (AV), which is carried by 90 per cent of the population.The virus had the normal CFTR gene inserted and had other harmful genes removed. Cystic fibrosis patients then inhale the GM virus into their lungs and the virus inserts the normal CFTR gene into the lung cells. Now for the first time the patient’s lung cells can produce a normal CFTR protein and hence can produce normal secretions on the lung surface. As the lung cells replace themselves, the GM virus would need to be inhaled on a regular basis. Whilst this gene therapy of cystic fibrosis is not a cure, it does reduce the chance of lung infections in the patients.Human trials have already begun into the other method in which liposomes are also used to transfer the genes.Liposomes consist of an artificial membrane (i.e. made in a microfuge tube and not by a living cell) filled with any cargo you want. A liposome can be used to deliver healthy CFTR genes into a cell.The liposome goes through a three step process when fusing with the plasma membrane of a cell and releasing its content into the cell. The liposome (red) is phospholipid bilayer that surrounds a drug or gene cargo (green). First the outer layer of the liposome fuses with the outer layer of the plasma membrane. Second, the two fused membranes coalesce as the inner layer of the liposome approaches the inner layer of the plasma membrane. Finally, the two inner layers fuse so that the drug or gene has access to the cytoplasm.Gene therapy is when new copies of defective genes are introduced into body cells.Why is cystic fibrosis a good candidate for gene therapy? Need to know the defective gene: in 1989 the gene was identifiedThere needs to be a need for the expensive treatment- current patients don’t have good therapy and CF is incurableNeed to be introduced- can easily be sprayed into lungsSUMMARYGE on human cells is called Gene Therapy. Genetic diseases such as cystic fibrosis are being treated using genetically engineered viruses. Cystic fibrosis patients have too much salt inside their cells which results in an osmotic imbalance and water entering the cells. The build-up of salt is due to a faulty cystic fibrosis transfer gene (CFTR gene).The adenovirus is the vector for transferring the healthy cystic fibrosis transfer gene (CFTR gene) into the lung cells of a CF patient.Once inside the cell, the healthy CFTR gene makes a protein that allows the cell membrane to allow salt to leave the cells to restore the correct water levels inside the lung cells.Problems associated with using adenoviruses to transfer the genes have seen the use of liposomes as an alternative method. ................
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