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Antisense Therapy

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Amber DiSanto

on 13 May 2011

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Transcript of Antisense Therapy

Antisense Therapy What is
Therapy? Antisense therapy is used for treatment for genetic disorders and diseases. Diseases are often connected to the short supply or overload production of certain proteins. If the production of these proteins is disturbed, many diseases can be treated or cured. In this therapy, a special synthesized stand of short RNA binds to mRNA product of the disease causing gene and deactivates it. When this deactivation occurs, it effectively helps stops the disease from reproducing and dies off. DNA is involved in Antisense technology by the process that occurs to help reproduce positive results to diseases like cancer. Antisense technology involves using Antisense nucleotides which are strings of RNA or DNA. These RNA strands bind to these ‘sense strands’ or the infected RNA strands to deactivate them. They have been used in research, and may become useful for therapy for certain diseases. Short antisenses strands of RNA can be introduced into cells, which then bind with target mRNA. How is DNA involved in this technology?
What is done to DNA in this technology? What does the technology look like? Provide a diagram or construct a model depicting the specific procedures and/or equipment use; e.g. the steps of the polymerase chain reaction (PCR) The process of synthesizing antisense nucleotides complementary to a required mRNA sequence is quite simple. After mRNA is made from the DNA strand, the mRNA binds to the sense or original mRNA sequence (which contains the disease). This mRNA antisense complex (disease carrying mRNA) can then no longer become a protein because it cannot move into translation and the diseased protein can no longer be produced. Advantages • A better understanding of the links between genetics, protein production and disease is expected to increase the impact of biotechnology on antisense technology.
• Antisense drugs can target a gene that is active in several types of cancers because they inhibit the production of the disease-causing proteins altogether.
• Antisense therapy could in our future be the end to cancer or other diseases. It might become one of the easiest processes to destroy cancer once perfectly developed.
• Antisense therapy is considered to be ‘modern biotechnology’. "Modern biotechnology refers to techniques that are used to intentionally manipulate genes, cells or living tissue in a predictable and controlled manner to produce new tissue or to generate changes in the genetic make-up of an organism." Disadvantages The antisense oligonucleotide must beat many obstacles before it can actually work and it is simple but complex process.
The antisense therapy is not a natural process, and it makes it hard for it to react with the body. The body has developed many defensive mechanisms to protect itself against foreign substances like the oligonucleotide. Researchers have found that adding sulfur atoms, methyl groups or a synthetic protein to the nucleotide backbone will help to protect the antisense from breakdown.
Another disadvantage is the antisense olignucleotide must enter the cell. This process can only be performed by making the strand neutral. Once in the cell, the antisense molecule must also avoid being trapped in the endosome compartments.
Once the antisense has be able to bind to the original affected mRNA, a hybrid forms. The hybrid then must destruct/destroy its target. (Studies show that this can occur through activation of the enzyme RNase H that breaks down the target.)
Antisense therapy is still in the trial and error process do to all the obstacles they scientists must overcome. The use of antisense drugs is not yet 100% developed and safe. I believe antisense therapy is a very interesting and new way to approach and help to reserve cancers, disease and etc. Even though many problems/obstacles have occurred like the way it reacts with the body, entering the cell and overall the struggle of being successful, i believe this is only because antisense therapy is only in its early stage of developement. With more and more research scientists will have the knowledge to almost perfect this process in many different ways.

As scientist believe that biotechnology could be the end or reversal of cancer and other diseases. This process targets this disease gene at one of the earliest reproduction stages possible and instead of treating it, it destroys it completely. This amazing technology could be the start too many other incredible discovers that might help us move further into finding the cure of cancer! How is the use of this technology regulated in Canada, and how does Canadian regulation of this technology compare to the regulation in another country, Canada has been interested in the antisense therapy research but has only recently taken part in the research.
USA was the first to invent this process of antisense therapy, it was discovered by a man named Paul Zamecnik. Today there are no Antisense drug therapies currently unavailable in Canada. There are many antisense therapies in development, which has been approved for use in the United States.

The United States seem to have a more developed process of antisense therapy and many positive outcomes have been present since the technology has been invented.
Canada is just as interested in the antisense therapy as the United States is. Kudos Paul Zamecnik was the inventor of the first antisense oligonucletiode in 1978. Paul C. Zamecnik was born in Cleveland, OH in 1912. He attended Dartmouth College, where he majored in chemistry and zoology and graduated with a bachelor's degree in 1933. He then went Harvard Medical School, received his M.D. in 1936. Then interned at the University Hospitals in Cleveland until 1939. He then started working at the Huntington Memorial Hospital of Harvard University at the Massachusetts General Hospital and became an Associate Professor of Medicine at Harvard Medical School. Later Zamecnik and Hoagland joined together and discovered a molecule that is essential for protein synthesis which was tRNA. By discovering tRNA it opened the door to many other interesting discoveries. Which then lead to the discovery of Antisense therapy (because of the similar concept). James D Watson and Francis Crick used an x-ray diffraction data collected, discovered by Rosalind Franklin to help discover the double helix or the DNA molecule in 1953. They were both rewarded the Nobel Prize is Physiology or Medicine in 1962.

Francis Crick was born in Northampton, England on June 8, 1916. James Watson was born on April 6 in 1928 in Chicago. At the age of 15, Watson was enrolled at Chicago University where he majored in zoology. In 1951, Watson joined Crick at Cavendish Laboratory in Cambridge, England. Watson was only 23 years of age when Crick and he discover the double helix. They came up with a method on how it is formed (heteroduplex).

Because of their discovery of the double helix, many scientists after them were able to discover out more about genes. One example is Paul Zamecnik. Many scientist in the past
are responisble for the incredible discovers for todays amazing scientific discovers. Rosalind Franklin, James Watson and Francis Crick were all scientists that contributed to the discovery of Antisense Therapy. James Watson and Francis Crick 1962 Paul Zamecnik James Watson and Francis Crick later in life Watson and Crick with the Double Helix What is one focused example of how genetic modification in applied in relation to the topic? One focused example of how genetic modification is applied in relation to Antisense therapy is cancer antisense therapy. Cancer antisense therapy is becoming more updated to target more specific biological pathways, cellular proteins and genetic components. The role of antisense therapy makes use of oligonucleotides to help with a potential treatment strategy in the fight against cancer. When the lab developed nucleotides, bind to these proteins, they make a heteroduplex. The antisense (or new genetically made strand) of mRNA will then bind to the matching nucleotides of the cancer's mRNA sense. Certain proteins like Bcl-2, IT-ras and PKC-alpha are just a few of the 20 proteins which are targeted. AffectedDNA
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