Gene Therapy and Cystic Fibrosis
One disease that gene therapy is used to treat is cystic fibroses. Cystic Fibroses is a genetic disease that affects the cells in the lungs, pancreas, and the small intestines and can cause infections of these organs [24]. Most people with Cystic Fibrosis if left untreated will not be likely to live past their 20s [24].
Cystic Fibrosis is caused by the mutation of the CFTR gene on chromosome 7 [2]. The normal CFTR gene is responsible for the productions of a protein channel called the cystic fibroses transmembrane conductance regulator [2]. This protein channel is found on the membranes of cells that produce mucus, sweat, saliva, tears and digestive enzymes [2]. This protein channel transports negatively charged chlorine particles into and out of the cell [2]. When chlorine ions exit the cell, it creates a concentration gradient and water diffuses through the cell membrane to the outside [2]. This ensures that the mucus that is produced is thin and free flowing [2]. The mucus that is produced lubricates and protects the lining of the airways, digestive system, reproductive system, and other organs by trapping the inhaled particles and bacteria [2]. The CFTR protein also regulates the functions of other protein channels such as the sodium channel which regulates the movement of sodium ions across the cell membrane [2]. The functions of these channels are essential in the normal functions of organs such as the lungs [2].
More than 1,000 mutations are found in patients with cystic fibrosis [2]. Most of these mutations involve the deletion of a small piece of DNA within that gene; this type of mutation is called frame shift mutation [2]. This mutation causes a change in the sequence of the protein that is created [2]. The most common mutation causes the amino acid at position 508 of the protein to be deleted [2]. The structure and stability of the abnormal protein channel that is produced is altered because of the mutation, in some cases, the protein is broken down before it is able to reach the cell membrane and do its job [2]. When this happens, chlorine ions cannot pass through the channels and water diffusion because of the change in concentration gradient seizes [2]. This affects the cells that produce mucus, causing the mucus that is produced to be thick and stick [2]. The thick mucus is no longer able to protect the cells from bacteria and it obstructs the airways and glands making the organs more susceptible to infections and causes the other symptoms of cystic fibrosis [2].
Gene therapy treats this disease by replacing the mutated gene CFTR with a normal gene [24]. Patients inhale the genetically altered Adenoviral vectors that carry normal CFTR strands through a nebulizer, a kind of inhaler [24]. The vectors then carry the normal gene to the affected cells and inject the gene into the cell [4]. Because the mutated CFTR does not affect the function of the normal protein channels, the newly inserted normal gene produces these protein channels and the channels can function normally [4]. This way, the cells can produce normal mucus and symptoms of cystic fibrosis do not occur [4]. Since this is somatic gene therapy, the effects of the therapy does not last for a very long time, therefore patients need to be treated regularly [4]. There are also some concerns regarding this therapy [4]. One of which is the possibility of the virus regaining its own DNA after entering the body which may cause the person to be infected with this virus [4].
Cystic Fibrosis is caused by the mutation of the CFTR gene on chromosome 7 [2]. The normal CFTR gene is responsible for the productions of a protein channel called the cystic fibroses transmembrane conductance regulator [2]. This protein channel is found on the membranes of cells that produce mucus, sweat, saliva, tears and digestive enzymes [2]. This protein channel transports negatively charged chlorine particles into and out of the cell [2]. When chlorine ions exit the cell, it creates a concentration gradient and water diffuses through the cell membrane to the outside [2]. This ensures that the mucus that is produced is thin and free flowing [2]. The mucus that is produced lubricates and protects the lining of the airways, digestive system, reproductive system, and other organs by trapping the inhaled particles and bacteria [2]. The CFTR protein also regulates the functions of other protein channels such as the sodium channel which regulates the movement of sodium ions across the cell membrane [2]. The functions of these channels are essential in the normal functions of organs such as the lungs [2].
More than 1,000 mutations are found in patients with cystic fibrosis [2]. Most of these mutations involve the deletion of a small piece of DNA within that gene; this type of mutation is called frame shift mutation [2]. This mutation causes a change in the sequence of the protein that is created [2]. The most common mutation causes the amino acid at position 508 of the protein to be deleted [2]. The structure and stability of the abnormal protein channel that is produced is altered because of the mutation, in some cases, the protein is broken down before it is able to reach the cell membrane and do its job [2]. When this happens, chlorine ions cannot pass through the channels and water diffusion because of the change in concentration gradient seizes [2]. This affects the cells that produce mucus, causing the mucus that is produced to be thick and stick [2]. The thick mucus is no longer able to protect the cells from bacteria and it obstructs the airways and glands making the organs more susceptible to infections and causes the other symptoms of cystic fibrosis [2].
Gene therapy treats this disease by replacing the mutated gene CFTR with a normal gene [24]. Patients inhale the genetically altered Adenoviral vectors that carry normal CFTR strands through a nebulizer, a kind of inhaler [24]. The vectors then carry the normal gene to the affected cells and inject the gene into the cell [4]. Because the mutated CFTR does not affect the function of the normal protein channels, the newly inserted normal gene produces these protein channels and the channels can function normally [4]. This way, the cells can produce normal mucus and symptoms of cystic fibrosis do not occur [4]. Since this is somatic gene therapy, the effects of the therapy does not last for a very long time, therefore patients need to be treated regularly [4]. There are also some concerns regarding this therapy [4]. One of which is the possibility of the virus regaining its own DNA after entering the body which may cause the person to be infected with this virus [4].