Once scientists determine the genetic cause for a diseases, that knowledge can potentially be used to find treatments and cures for the disorder. There are several mechanisms that are currently being researched as possible genetic treatments of the future.


One treatment mechanism is through a little molecule called RNA interference, or RNAi. Much like turning off a light switch, RNA interference (RNAi) offers the ability to selectively silence or “turn off” the activity of a single gene. This technology has the potential to revolutionize our understanding of how genes work and offers new promise in therapy and treatment.


Messenger RNA (mRNA), a copy of the instruction containing part of the DNA that is single stranded, is created in the nucleus, but travels to the ribosome to direct the protein’s creation. The amount of mRNA produced for a specific gene can be correlated with the amount of protein that will be made – more mRNA usually leads to more protein.


Other types of RNA are also present in cells. Researchers in the 1990s noted an additional form of RNA composed of small double-stranded molecules. These fragments could effectively stop protein production by coordinating the destruction of the single stranded mRNA. In other words, the double stranded RNA “interfered” with the mRNA, effectively silencing the activity of the gene.


Researchers have utilized the RNAi pathway to explore the effects of systematically silencing genes. Short synthetic double-stranded RNA molecules can be created in the laboratory and delivered to cells, leading to the partial or complete cessation of protein production. The ability to target and deplete specific proteins has also identified RNAi as a potential therapeutic pathway. One of the first RNAi therapies to enter clinical trials focused on a form of age-related macular degeneration, a disorder that destroys central vision. Macular degeneration is influenced by excessive levels of a protein that promotes blood vessel development behind the retina. These vessels can leak, leading to the vision loss. In a series of remarkable clinical trials, short fragments of double-stranded RNA that target the mRNA for this protein were injected directly into the eyes of affected individuals. Although intended primarily to assess safety issues, the initial trial results were promising. Two months after injection with the drug, a quarter of the patients experienced significantly clearer vision, while the vision of the other patients had stabilized.


Learn more about RNAi and its possible role in disease treatment at this interactive site http://www.pbs.org/wgbh/nova/sciencenow/3210/02.html. There is a good animation that explains what RNAi is and how it works within the cell.

Gene Therapy

Another possible mechanism for treatment of genetic diseases is through gene therapy. The goal of gene therapy is to actually modify a person’s genetic material in effort to correct a genetic mutation causing a disease. A corrected version of the disease causing gene is inserted into cell’s in the patient’s body. This corrected gene can now allow the cells to produce the proteins that the body was lacking and could correct problems associated with the disease.


DNA itself is not capable of getting through cell membranes into the cells. Instead, the corrected gene (therapeutic gene) must be inserted into a type of vector which can transport the DNA into the host’s cells. The most commonly used vector is a virus because viruses have the capability to get into a cell and replicate. All the harmful genes are removed from the virus’ genome and the therapeutic gene is inserted.


What are some of the potential problems or hurdles with gene therapy? One issue is that it is hard to get the corrected gene into the right cell type in the right tissue. If the problem is in the lungs, it will do no good having the corrected gene producing protein in the patient’s brain. There are also issues on the molecular level. Once the gene is inserted into the right cells it has to be “turned on” for protein production to occur. This can be difficult to orchestrate in real life.


Depending on the type of vector used, the gene may be inserted into the cellular genome or it may remain outside the nucleus as an episome (genetic material in the cytoplasm that replicates independently). There are benefits and problems with each type of placement. If the gene integrates into the host genome it will then be passed on when the cell divides producing long-term expression. However, there is the potential for the gene to be inserted into a position in the genome that would alter another necessary gene causing negative effects. The human immune system, which is supposed to find and eliminate harmful viruses, can pose an obstacle for gene therapy viral vectors. Also, in some diseases simply adding a corrected gene will not fix the problem because the mutated copy that is still present may prevent it from helping.


This therapy will not work for all diseases. The best potential for gene therapy treatment are in those disorders that are caused by a mutation in a single gene.


Cystic fibrosis is a disease that is ideal for treatments such as gene therapy. It is caused by a mutation in a single gene CFTR which produces a chloride channel. It has also been determined that a person with just 5-10% of the normal level have a good clinical outcome. There have been many gene therapy clinical trials on gene therapy of cystic fibrosis, but so far none have had a good enough response for clinical applicability. Aerosol inhalers have been used to get the vectors to the lungs. However, there have been significant problems getting through the mucus that covers the lung epithelial cells in cystic fibrosis patients.


Another disorder that has had attempts at gene therapy is muscular dystrophy. This is also a disease caused by a mutation in a single gene (dystrophin). The problems that arose were the fact that the dystrophin gene is too large for many vectors. Also, there is not a single cell type that needs to be targeted for therapy. Skeletal muscle cells need the therapy, as well as the heart and diaphragm which are much harder to target.


To learn more about gene therapy and its potential as a genetic treatment option go to http://learn.genetics.utah.edu/units/genetherapy/. This is a great website with much information.