How rna interferecne

The discovery of ribonucleic acid interference has sparked a wave of enthusiasm in the scientific community. Since the discovery of RNA interference scientists have used it to identify the molecular processes of different diseases. RNA interference has the potential to be used in a wide range of applications one of which is cancer therapies. The unique key to RNA interference as it does have any of the side-effects normally attributed to the cure of these diseases. This is because it does not replicate the function of the degenerated part of the body but it prevents the degeneration is the first place. However there is always a problem with adding synthetic materials to the human body. Firstly we can not truly know how they wil react until they are used and secondly they cause a mutation in the part of the human body they are implanted it causes that part to become inactive. We wil also look at and try to weigh up the issues raised with this kind of revolutionary treatment and the possible ways it could be used to increase the length and quality of life. We wil all suffer from hundreds of different il ness at some point in our lives; the severity of which can range from the common cold to an il ness that can threaten our lives. Some of these il nesses are easier for our immune system to fight off than others and a few we are al but defenseless against. As technology has developed scientists have slowly found ways to cure or prevent us from becoming il mainly by the use of vaccinations. A vaccination is an injection of a kil ed microbe they are used in order to stimulate the immune system against the microbe, thereby preventing disease. Now we are faced with increasingly harder chal enges, as these il nesses mutate to become immune to our defenses and the range of medicines we use against them. Some diseases that are becoming increasingly hard to treat with antibiotics are tuberculosis, gonorrhea, pneumonia and septicemia. This is due to the increasing use of existing antibiotics in human and veterinary medicine and also in agriculture. A new way for us to fight these il nesses is RNA interference. RNA is a nucleic acid similar to DNA but contains ribose rather than deoxyribose. It forms on the template strand of DNA. RNA interference is believed to be able combat illnesses such as cancers, viruses and neurodegenerative disease which is becoming more and more frequent as life expectance is increasing. This double strand RNA (dsRNA) is used as a viral defense in plants and invertebrates but not in humans. RNA interference was discovered in 1998 by two scientists, Andrew Fire and Craig Mello. Using nematode worms Caenorhabditis elegans, they investigated how gene expression is regulated. During there experiments they discovered that when they injected both ―antisense‖ RNA and ―sense‖ RNA together they joined to form double strand RNA (dsRNA). dsRNA Long strands of this dsRNA trigger the interferon reaction, but short strands RNA (siRNA) trigger the interferences response. This siRNA is most commonly between 19 and 23 nucleotides in length. Tests have revealed that the dsRNA seemed to silence the gene carrying the same code as the dsRNA. The possible uses of this are vast not only for humans but for al mammals. This means it has both interest from the medical and veterinary professions. This would also al ow us to use antibiotics less frequently which would slow the resistance of some bacteria. It could also be use to destroy cancers, neurodegenerative diseases, virus that alter the hosts DNA, such as hepatitis Band parvovirus B19. In the case of cancer there were 12.2 mil ion reported cases of which 7.5 mil ion people died worldwide every year. With neurodegenerative diseases there are more than 20 mil ion new cases every year. Unfortunately as with every new scientific discovery there are several ethical issues that must be taken into account and if possible over come before the therapy can become available to the public. This paper wil focus on preventing the development of neurodegenerative diseases mainly Parkinson’s diseases. It is not yet clear whether Parkinson’s is a genetic disease or not. In some families there are some specific genetic abnormalities that have been shown to lead to the disease but in the majority of cases the genetic abnormalities are not present. Parkinson’s disease is caused by a lack of dopamine which is produced by neurons in the substantia nigra. The dopamine serves as a chemical messenger in the brain and al ows communication between the substantia nigra and the corpus striatum. These two areas of the brain coordinate to al ow smooth and balanced muscle movement. A lack of dopamine results in abnormal nerve functioning, causing a loss in the bodies’ ability to control movement. The symptoms of Parkinson’s disease usual y begin slowly and develop gradual y over time. Parkinson’s effects people differently and the symptoms do not show in a particular order. There a three main symptoms for Parkinson’s. Firstly, bradykinesia this is a slowness of movement and a loss of movement coordination. Secondly tremors this shaking wil often occur first in the hands or arms and wil become more noticeable with time. The final, symptom is a stiffness of the muscles with wil make performing simple everyday tasks hard. This disease and others like it is becoming increasingly present as life expectance is increasing. As medical science develops the life expectance of our species increases. As it does so we are seeing more and more cases of neurodegenerative diseases such as Huntington’s, Alzheimer’s and Parkinson’s. Nobody knows for sure whether a medical disorder is caused by genetics or not until it is specifically tested for. It is possible for relative’s to experience the same neurodegenerative diseases and not to have inherited it. Neurodegenerative diseases normal y occur due to a mutation in the DNA during division. Which results in a protein being synthesised with a different amino acid in the code with causes it shape to change due to the formation of different bonds. This strand of protein is synthesised in the ribosome and are coded for by messenger RNA (mRNA). mRNA is a type of RNA that reflects the exact nucleoside sequence of the genetical y active DNA. mRNA carries the ―message‖ of the DNA to the cytoplasm of the cel s where protein is made in amino acid sequences specified by the mRNA. To form mRNA the double helix of DNA must uncoil and open out in doing so the hydrogen bonds between the template and coding strand break. Free RNA nucleotides then join to the complimentary bases on the template strand of DNA. The arrangement of these bases wil determine the chain of amino acids produced by the ribosomes. The change in the one of the base pairs will result in a different amino acid being produced. This could result in the protein folding in a different way that wil cause it to be unable to perform the function it was designed for. The possibility of these mutations being destroyed by our bodies’ immune system wil at the very least slow the degeneration of the neurons which would al ow movement control to be effective for longer. The most common treatment taken by people suffering from Parkinson’s disease at present is a medicine that replaces dopamine. These medicines are a combination of levodopa, which is broken down in the formation of dopamine and another chemical which ensures the levodopa reaches the brain. Although this option is a long term treatment for people suffering from Parkinson’s it does come with side-affects such as feeling sick, vomiting and sudden sleepiness in the short term. There are some long term problems such as unwanted movement of the face and limbs (dyskinesia). Many of these treatments can become less reliable over time. This wil become more of a problem as life expectance increases as people RNA Interference should not give any side-effects to the user as it wil prevent the degeneration of the neurons in the substantia nigr rather than try to replace there function once they are no longer working. The problem with using RNA interference to prevent the degeneration of cel s in the human body is unlike a virus the degeneration of these cel s in the body can happen in a number of ways. Some of these ways may not yet have been identified as a cause of the disease. Unlike degeneration a virus will only alter the DNA in one specific way which can easily be targeted. With degeneration the thing you must remember is that it is not one specific change in the DNA that you are looking for but instead you are trying to prevent a combination of any variety of changes that could or could not be responsible for the degeneration. Another obstacle that must be over come is that, the degeneration can happen at any point so al the possible variations of the dsRNA must remain in al the possible effected cel s for the duration of the individuals life. This make the job of preventing the degeneration that much harder. Bearing this in mind it would be much more effective if the specific dsRNA code to then be adapted in to the process of cel division so that the dsRNA code does not need to be re-administered. This would mean that every new cel in our body would then be able to pass it on to its daughter cel . The problem that could then occur is the one that we were trying to prevent in the first place, if the implanted dsRNA code was to mutate during the cel division it would then be ineffective against the virus or the specific mutation it was targeted at. This could result in the degeneration stil occurring or in the case of a virus the host wil become infected. In the worst case it could mutate into something that is vital to the cel s survival and would destroy We can determine the problems that would be encountered with trying to add the synthetic dsRNA into the division process by looking at the work done by Chemists and synthetic biologists to see if they can expand the genetic code of proteins, with unnatural nucleotides that can be incorporated into DNA and RNA sequences and unnatural amino acids that can expand the chemical functionality of proteins. These amino acids can make the bonds inside the protein more stable which wil al ow them to be able to survive in harsher environments or add new chemical groups which wil al ow the protein to do new biochemical reactions. They are trying to do this by making a whole paral el genetic code in a living cel . This is designed to use evolution to direct a ribosome that can read four letter codons instead of the normal three. These problems range from being unable to accurately determine the way in which the synthetic dsRNA code wil interact with the DNA already present in the cel . This could result in the normal function of the DNA being interrupted and vital protein chains no longer being synthesized. This would devastate the function of the cel causing unknown damage. This wil also be majorly affected by the publics view on this, after al it is being developed to help the general public and many could view the change being made to the cel s as scientists ―playing God‖ this would be hard for people to come to grips with and only with the support of the public can this project have any change in helping people to survive viruses and prevent Nero degeneration. If we somehow manage to add synthetic dsRNA codes into the nucleus of a cell in a way in which it can be incorporated into the cell without causing any changes to the existing DNA. Along with being able to incorporate it into the division process so that the original cel can pass a copy on to each of the daughter cells. Once al of this has been achieved a new problem wil arise and this is one of space. There is only a finite amount of space inside the nucleus of a cel some of which is already occupied by the chromosomes. If we can find a way to introduce a dsRNA that can be used to prevent al the possible different viruses and the degeneration of a specific part of the body would it be possible of that specific dsRNA code to just be present in the required area. For instance the dsRNA code that prevent the degeneration of the neurons in the substantia nigra this is the only place it wil need to be present. For instance the dsRNA code that prevent the degeneration of the neurons in the substantia nigra this is the only place it wil need to be present. This could be possible if we passed these dsRNA with the genetic coding of the parent to the offspring. These stem cel s will then divide and specialize into the different tissues in the body. This would be the perfect way in which to ensure the specific dsRNA only went to the area that they where required eliminating the problem of over whelming the cell with too much genetic information. For some of the viruses that we are trying to arm ourselves against wil only become a threat to us at certain points in our lives. However if the dsRNA code stays present in our cel s for the whole of our lives this presents us with a much greater chance of a mutation that could become ineffective or that could cause damage to the natural function of the cel . This is where being able to introduce and take out the dsRNA codes when necessary wil greatly increase the chance of success. Another problem that must be over come before the wide spread use of RNA interference is that with adding the dsRNA into the cel is that once it has been introduced into the division process it wil become just as susceptible to mutations as normal unaltered DNA. This could then cause a problem as we would make dsRNA that wil code for the possible mutations in the primary dsRNA code al of this would result in a never ending circle unless we find a way in which we can produce the dsRNA so that it is resistant to mutations. The shorter the dsRNA code needed the less likely it wil be to mutate. The support of the general public is stil the one necessity that wil underpin the success of this project. One of the problems that must be over come is that the public seems to have a distrust of scientist with the view that they are trying to ―play god‖ by altering thing that should ultimately not be ours to change. People could also see it as fundamental y changing who we are by adding thing to our DNA that are not natural y occurring. These issues must be weighed up against the fact that this new treatment could have the potential to cure al forms of cancer, every virus and prevent the degeneration of our cel as we age. For this project to take off the public must believe that the benefits out weigh the risks and that by adding the dsRNA codes into the body it does not change who we are. This is vital as ultimately the only way to be sure if the dsRNA code work with out side-effects is to put it in to practice and test is on people that are suffering from things such as cancer and hepatitis B. To be able to do this we need the backing of the public and people that believe in it enough to put them selves forward to trail the RNA interference. RNA interference is a fantastic and exiting new way in which the medical and veterinary profession can strive to improve the quality and length of peoples and animals lives. The possibility that the dsRNA can be introduced to the body in a way that wil al ow them to natural y spread wil illuminate the problem of maintaining the levels for the needed time. If it is possible for the dsRNA to be passed from the mother and farther to the child it is possible that when the stem cel s specialize the dsRNA specialize to this wil mean that getting the dsRNA to the relevant area of the body becomes easier. The only problem is trying to ensure that the dsRNA specialize to the desired area of the body where they can be used most effectively. The development of this treatment is very important as the potential number of life that it can save is vast and as life expectance increases these figures will rise. We already know the specific mutation or change to the hosts DNA caused by several viruses that occurs resulting in a cancerous growth or the infection of a virus. We now must synthesis a dsRNA code that can successful y be used to il uminate the undesired code to prevent it from using our cel s to reproduce. Whilst doing this we must introduce the idea for this treatment to the general public to al ow them time to come to grips with the issues and possible successes of this project as secrecy wil ultimately only lead to suspicions and once this treatment has been properly developed we will need people that are suffering form these cancers and viruses to have enough support and belief in this treatment to be involved in the trial and hopeful y long term use of this treatment. Posted on: February 18, 2010 7:10 PM, by Error! Hyperlink reference not valid.
Parkinson's disease, Published by Bupa's health information team, April 2009 Edited by Cynthia Dennison Haines, MD on June 01, 2005 6. THE EUAN MACDONALD CENTRE FOR MOTOR NEURONE DISEASE RESEARCH THE UNIVERSITY OF EDINGBURGH CAMPAIGH Andrew Fire and Craig Mello won the Nobel Prize in Physiology or Medicine for 8. How Many People Die from Cancer Each Year 9. Pete Kennedy and Frank Sochacki, OCR biology AS, Heinemann publishing group 14. Lectures in Microbiology by Kenneth Todar PhD, 2009, University of Wisconsin-

Source: http://synergysolutions.org.uk/Workshop/vetpathology/JewersR.pdf