Responsible for the Production of Protein PCSK9
The primary objective of the media review project is to have the student analyze the differences and similarities in the way that news papers and journals present new discoveries to the world. On November 11, 2008, The New York Times published "The Promise and Power of RNA", which disscussed the use of RNA interference(RNAi) to silence PCSK9(Proprotein Convertase Subtilisin/Kexin type 9), a protein that has been associated with high risk of heart attack and high cholesterol. The article also discusses different drugs made using RNAi, such as Alnylam, an inhalable drug that could be a possible treatment for respiratory viruses. The article focuses on how RNAi can be used to lower cholesterol, and the risk of heart attack. On August 13, 2008, the Journal of Proceedings of the National Academy of Sciences of the United States of America(PNAS) published "Therapeutic RNAi targeting PCSK9 acutely lowers plasma Cholesterol in Rodents and LDL Cholesterol in nonhuman Primates". I will be analyzig the similarites and differences between these two articles.
Mechanism for Gene Splicing with RNA Interference
Analyzing Both Articles
2)The journal article had a results section instead of a conclusion section. In the results section the experiementors highlighted that this method of treatment is so far only tested in rodents and then tested in humans and it was about to decrease the transcription of PCSK9 greater than 70%. Their experiement showed that siRNA was capapble of silencing the human transcript and subsequently reducing the amount of circulation plasma human PCSK9 protein and that the development of RNAi therapeutic drugs will be effective.
3)The journal article did not discuss any uncertainties but the news article did. The news article stated that although it will be a great drug to develop but because RNAi uses double-stranded RNA it will not be accepted by the cell easily, and the small RNA snippets might silence genes beyond the intended target, therefore the treatment might not be possible.
4)The journal article only focused on the use of RNAi to lower cholesterol and the risk of heart attack. While the news article discussed the broader implications of RNAi in the development of therapeutic drugs. The news article stated that scientists have found some micro-RNAs that contribute to the formation of cancer and RNAi could be used to silence the gene. Also scientists lately have been finding different types of RNA besides mircor-RNA(miRNA),), the new ones include small interfering RNA (siRNA), piwi-interacting RNAs (piRNA), chimeric RNA, and promoter-associated and termini- associated long and short RNAs. They join an existing stable that included messenger RNA (mRNA), transfer RNA (tRNA), and small nucleolar RNA (snoRNA), which all play roles in protein production. Also Scientists do not know the use of the newly founded RNAs and some scientist believe that it could be the byproduct of other cellular processes. But if the uses of these RNA are found then RNAi could be used to regulate any negative effects they have. The news article pointed out that when RNAi was directed at the promoters of genes, instead of silencing it caused the genes to become more active and protein production increased. This was an experiement carried out by Dr. Corey. This shows that RNAi has a lot of possibilities.
5)The introduction of the journal article doesn't discuss any past contradictory work to their experiement.
6)As discussed in number 4 the news article discusses the use of RNAi not only as a gene silencer but also as a way to increase the amount of protein produced when RNAi is directed by the promoter of the gene.
Related Articles for Further Investigation of RNAi
Source: Utilizing RNA Interference to Enhance Cancer Drug Discovery by Elizabeth Lorns, Christopher J. Lord, Nicholas Turner and Alan Ashworth.
More about RNA Interference
RNA interference was first discovered in 1998 by Andrew Fire and Craig C. Mello, who were working with the nematode Caenorhabditis elegans. They received th Nobel Prize for their great breakthrough in Physiology or Medicine in 2006.
Many diseases have the potential to be cured or attenuated with RNAi—cancer, neurologic disorders such as Huntington’s disease, viruses, macular degeneration, and more. The concept is simple: Insert a double-stranded sequence of a gene or protein that is essential to the disease’s survival in the cell. Interfering RNA will bind to the invading double strand and destroy it as well as endogenous mRNA sequences coding for that gene or protein. The disease will not be able to survive because a vital element has been destroyed.
It seems like a very simple process but in reality, researchers have run into problems. In mammals, long pieces of double-stranded RNA automatically trigger an interferon response (a natural defense protein that destroys invading substances such as viruses, bacteria, parasites, and tumor cells9), which is normally a good thing. But if the exogenous dsRNA is destroyed before the RNAi process begins, it obviously can’t go about its job of destroying targeted endogenous mRNA strands. Researchers have discovered that if they design siRNAs that are shorter than 30 nucleotides long and insert them into a cell, they will be short enough to avoid the cell’s interferon response.
So research continues to see whether RNAi will be the potent therapy that it has the potential to be.
A good animation of the RNAi process is shown atHERE
1)The news article claims that scientists believe that RNA interference evolved as a way to fight viruses because double-stranded RNA is rare outside viruses. The article also claims that with the silencing of the gene that is responsible for the production of PCSK9, a therapeutic use could be found for it to lower cholesterol and lower the risk of heart attack. The article continues to explain that although this is a geat idea it is hard to accomplish because the small RNA snippets might silence genes beyond the intended target. Also because double-stranded RNA is rare outside viruses, the cell will not likely accept the RNA; this makes having the treatment for mass use very impossible. The journal article supports only the second claim.
