- Basic Concepts
- DNA & RNA
- Simple Inheritance
- Modify Mendelian Ratios
Gene therapy is a method for treating genetic diseases. It is based on the principle that faulty genes, those with mutated DNA sequences, can be replaced with the "correct" gene within a cell. Therefore, the disease can be stopped or cured.
The process of gene therapy involves the use of vectors. Vectors, in most cases, are viruses that have been scientifically modified to serve as transporters of the healthy gene. The vector works to insert the healthy gene into the cell in order to replace the mutated DNA. Each vector carries a "correct" form of the DNA sequence.
Depending on the type of cell that is carrying the mutated gene, different vectors are used. Examples of virus vectors are the adenovirus and retrovirus. The adenovirus is used to infect nondividing cells, and it inserts the healthy gene into the cytoplasm. Therefore, it only works for a certain length of time before it is degraded by the cell. The retrovirus is used to infect dividing cells, and it inserts the healthy gene into the nucleus of the cell. Since it is incorporated into the nucleus, there is an unlimited amount of time that the phenotype of the healthy gene will be expressed.
Gene therapy can be administered by either in vivo or ex vivo processes. The in vivo process involves the insertion of healthy genes into cells at the site at which they are found in the patient. For example, patients with cystic fibrosis can inhale an adenovirus vector to try to correct the defective gene in their lungs. The ex vivo process involves the removal of cells from the patient, inserting the healthy genes via vectors, and then returning the treated cells back into the patient. An example of the ex vivo process would be the removal of stem cells from the bloodstream. The stem cells are given the correct DNA sequence and then returned to the bloodstream, so as they divide they produce blood cells with the correctly functioning gene.
Gene therapy can be classified by the type of cell being used, namely somatic (body cell) or germline (sperm or egg) cell, and by the type of DNA being altered, either nuclear or mitochondrial. Somatic cell therapy treats the genetic disease in the individual patient and its effects are not carried over to the progeny. This means that the progeny can still inherit the mutant form of the gene. Germline cell therapy cures the disease because it changes the DNA sequence of the gene at the reproductive level. Therefore, progeny cannot inherit the mutated form of the gene, and future generations will not experience the disease. Germline cell therapy is not practiced in humans, though it has been tested in animals, because of the ethical issues that arise from it and the uncertainty of its long-term effects.
Recently, scientists who were trying to improve the eggs of infertile women by infusing them with cytoplasm from the eggs of fertile donor women made a startling discovery: the cells of two of the children born as a result of this technique had mitochondrial DNA from both their mother and the donor egg. This meant that when the cytoplasm was transferred from the donor egg to the mother's egg, it contained some mitochondria as well. This result has exciting possibilities for gene therapy. Since some diseases are caused by mutations in mitochondrial DNA, it may be possible to correct these gene defects by simply injecting normal mitochondria into an egg before fertilization or by placing the nucleus of a mother's egg into a donor female's cytoplasm. However, since the new mitochondria can be found in every cell of the recipient's body, and thus could be passed on to their offspring, ethical concerns are being raised about this type of gene therapy as well.
There are several problems with gene therapy that currently prevent it from being a frequently used treatment.
1. Many diseases are polygenic, meaning that they are caused by multiple genes. Therefore, the exact involvement of each gene and the proteins or enzymes they code for must be figured out in order for the treatment to be effective.
2. A large number of cells must be taken from the patient and harvested because vectors are not always efficient. In many cases, only one cell in a thousand or greater will receive the correct form of the DNA from the vector. Methods for collecting cells and increasing the amounts harvested must be optimized.
3. It is not always probable that the vector will find the mutated cells, and if it does, it is not certain that the DNA sequence will be expressed. Therefore, better vectors must be developed that can successfully find the faulty cells and insert the DNA sequence accurately.
Once these problems and other factors not yet understood are worked out, gene therapy should be an effective way to treat genetic diseases.