The vaccine made history not only because it reported a 95 percent efficacy rate at preventing COVID-19 in clinical trials, but because it is the first vaccine ever approved by the FDA for human use that is based on RNA technology.<\/p>\n
\u201cThe development of RNA vaccines is a great boon to the future of treating infectious diseases,\u201d says Lynne Maquat<\/a>, the J. Lowell Orbison Distinguished Service Alumni Professor in biochemistry and biophysics, oncology, and pediatrics at Rochester and the director of Rochester\u2019s Center for RNA Biology.<\/p>\n COVID-19, short for \u201ccoronavirus disease 2019,\u201d is caused by the novel coronavirus SARS-CoV-2. Like many other viruses, SARS-CoV-2 is an RNA virus. This means that, unlike in humans and other mammals, the genetic material for SARS-CoV-2 is encoded in ribonucleic acid (RNA). The viral RNA is sneaky: its features cause the protein synthesis machinery in humans to mistake it for RNA produced by our own DNA.<\/p>\n For that reason, several of the leading COVID-19 vaccines and treatments are based on RNA technology.<\/p>\n A contingent of researchers at the Ä¢¹½´«Ã½<\/a> study the RNA of viruses to better understand how RNAs work and how they are involved in diseases. This RNA research provides an important foundation for developing vaccines and other drugs and therapeutics to disrupt the virus and stop infections.<\/p>\n \u201cUnderstanding RNA structure and function helps us understand how to throw a therapeutic wrench into what the COVID-19 RNA does\u2014make new virus that can infect more of our cells and also the cells of other human beings,\u201d Maquat says.<\/p>\n RNA stands for ribonucleic acid.<\/p>\n RNA delivers the genetic instructions contained in DNA to the rest of the cell.<\/p>\n Covid-19 stands for “coronavirus disease 2019.”<\/p>\n<\/div>\n In the past few decades, as scientists came to realize that genetic material is largely regulated by the RNA it encodes, that most of our DNA produces RNA, and that RNA is not only a target but also a tool for disease therapies, \u201cthe RNA research world has exploded,\u201d Maquat says. \u201cThe Ä¢¹½´«Ã½ understood this.\u201d<\/p>\n In 2007, Maquat founded The Center for RNA Biology<\/a> as a means of conducting interdisciplinary research in the function, structure, and processing of RNAs. The Center involves researchers from both the River Campus and the Medical Center, combining expertise in biology, chemistry, engineering, neurology, and pharmacology.<\/p>\n \u201cOur strength as a university is our diversity of research expertise, combined with our highly collaborative nature,\u201d says Dragony Fu<\/a>, an associate professor of biology on the River Campus and a member of the Center for RNA Biology. \u201cWe are surrounded by outstanding researchers who enhance our understanding of RNA biology, and a medical center that provides a translational aspect where the knowledge gained from RNA biology can be applied for therapeutics.\u201d<\/p>\n A graphic created by the New York Times<\/a> illustrates how the coronavirus that causes COVID-19 enters the body through the nose, mouth, or eyes and attaches to our cells. Once the virus is inside our cells, it releases its RNA. Our hijacked cells serve as virus factories, reading the virus\u2019s RNA and making long viral proteins to compromise the immune system. The virus assembles new copies of itself and spreads to more parts of the body and\u2014by way of saliva, sweat, and other bodily fluids\u2014to other humans.<\/p>\n \u201cOnce the virus is in our cells, the entire process of infection and re-infection depends on the viral RNA,\u201d Maquat says.<\/p>\n One of the reasons viruses are such a challenge is that they change and mutate in response to drugs.<\/p>\n That means novel virus treatments and vaccines have to be created each time a new strain of virus presents itself. Armed with innovative research on the fundamentals of RNA, scientists are better able to develop and test therapeutics that directly target the RNAs and processes critical to a virus\u2019s life cycle.<\/p>\n Traditional vaccines against viruses like influenza inject inactivated virus proteins called antigens. The antigens stimulate the body\u2019s immune system to recognize the specific virus and produce antibodies in response, with the hope that these antibodies will fight against future virus infection.<\/p>\n RNA-based vaccines\u2014such as those developed by Pfizer\/BioNTech and American biotechnology company Moderna\u2014do not introduce an antigen, but instead inject a short sequence of synthetic messenger RNA (mRNA) that is enclosed in a specially engineered lipid nanoparticle. This mRNA provides cells with instructions to produce the virus antigen themselves.<\/p>\n Once the mRNA from a vaccine is in our body, for example, it \u201cinstructs\u201d the protein synthesis machinery in our cells, which normally generates proteins from the mRNAs that derive from our genes, to produce a piece of the SARS-CoV-2 virus spike protein. Since the SARS-CoV-2 virus spike protein is foreign to our bodies, our bodies will then make antibodies that inactivate the protein.<\/p>\n \u201cShould the virus enter our body from an infected person, these antibodies will bind to and inactivate the virus by binding to its spike proteins, which coat the outside of the viral capsule,\u201d Maquat says.<\/p>\n An RNA-based vaccine therefore acts as a code to instruct the body to make many copies of the virus protein\u2014and the resulting antibodies\u2014itself, resulting in an immune response.<\/p>\n Unlike more traditional vaccines, RNA-based vaccines are also beneficial in that they eliminate the need to work with the actual virus.<\/p>\n \u201cWorking with a live virus is costly and very involved, requiring that researchers use special biosafety laboratories and wear bulky personal protective equipment so that the virus is \u2018biocontained,\u2019 and no one gets infected,\u201d Maquat says.<\/p>\n Developing a vaccine from a live virus additionally takes much longer than generating an mRNA-based vaccine, but \u201cno one should think the process is simple,\u201d Maquat says of the Pfizer\/BioNTech vaccine. \u201cSince it is the first of its kind, a lot had to be worked out.\u201d<\/p>\n Maquat has been studying RNA since 1972 and was part of the earliest wave of scientists to realize the important role RNA plays in human health and disease.<\/p>\n Our cells have a number of ways to combat viruses in what can be viewed as an \u201carms race\u201d between host and virus. One of the weapons in our cells\u2019 arsenal is an RNA surveillance mechanism Maquat discovered called nonsense-mediated mRNA decay (NMD).<\/p>\n \u201cNonsense-mediated mRNA decay protects us from many genetic mutations that could cause disease if NMD werenot active to destroy the RNA harboring the mutation,\u201d she says.<\/p>\n Maquat\u2019s discovery has contributed to the development of drug therapies for genetic disorders such as cystic fibrosis, and may be useful in developing treatments for coronavirus.<\/p>\n \u201cNMD also helps us combat viral infections, which is why many viruses either inhibit or evade NMD,\u201d she adds. \u201cThe genome of the virus COVID-19 is a positive-sense, single-stranded RNA. It is well known that other positive-sense, single-stranded RNA viruses evade NMD by having RNA structures that prevent NMD from degrading viral RNAs.\u201d<\/p>\n Maquat\u2019s lab has been collaborating with a lab at Harvard University to test how viral proteins can inhibit the NMD machinery.<\/p>\n Their recent work is focused on the SARS-CoV-2 structural protein called N. Lab experiments and data sets from infected human cells indicate this virus is unusual because it does not inhibit the NMD pathway that regulates many of our genes and some of the virus\u2019s genes. Instead, the virus N protein seems to promote the pathway.<\/p>\n \u201cSARS-CoV-2 reproduces its RNA genome with much higher efficiency than other pathogenic human viruses,\u201d Maquat says. \u201cMaybe there is a connection there; time will tell.\u201d<\/p>\n In the Department of Biology, Fu and\u00a0Jack Werren,<\/a> the Nathaniel and Helen Wisch Professor of Biology, received expedited funding awards from the National Science Foundation to apply their expertise in cellular and evolutionary biology to research proteins involved in infections from COVID-19. The funding was part of the NSF\u2019s Rapid Response Research (RAPID) program to mobilize funding for high priority projects.<\/p>\n Werren\u2019s research will be important in ameliorating some of the potential side effects of COVID-19 infections, including blood clots and heart diseases, while Fu\u2019s research will provide insight into the potential effects of viral infection on human cell metabolism.<\/p>\n \u201cOur research will provide insight into the potential effects of viral infection on host cellular processes,\u201d Fu says. \u201cIdentifying which cell functions are affected by the virus could help lessen some of the negative effects caused by COVID-19.\u201d\u00a0 Green = said twice.<\/p>\n Douglas Anderson<\/strong><\/a>, an assistant professor of medicine in the Aab Cardiovascular Research Institute and a member of the Center for RNA Biology, studies how RNA mutations can give rise to human disease and has found that alternative therapeutics, such as the gene-editing technology CRISPR, may additionally \u201cusher in a new approach to how we target and combat infectious diseases,\u201d he says.<\/p>\n For the past few years, Anderson\u2019s lab has developed tools and delivery systems that use the RNA-targeting CRISPR-Cas13 to treat human genetic diseases that affect muscle function. CRISPR-Cas13 is like a molecular pair of scissors that can target specific RNAs for degradation, using small, programmable guide RNAs.<\/p>\n When the health crisis first became apparent in Wuhan, China, researchers in Anderson\u2019s lab turned their focus toward developing a CRISPR-Cas13 therapeutic aimed at SARS-CoV-2. Applying the knowledge already available about coronavirus RNA replication, they designed single CRISPR guide RNAs capable of targeting every viral RNA that is made within a SARS-CoV-2 infected cell. Using a novel cloning method developed in Anderson\u2019s lab, multiple CRISPR guide-RNAs could be packaged into a single therapeutic vector (a genetically engineered carrier) to target numerous viral RNA sites simultaneously. The multi-pronged targeting strategy could be used as a therapy to safeguard against virus-induced cell toxicity and prevent \u2018escape\u2019 of viruses which may have undergone mutation.<\/p>\n \u201cInfectious viruses and pandemics seemingly come out of nowhere, which has made it hard to rapidly develop and screen traditional small molecule therapeutics or vaccines,\u201d Anderson says. \u201cThere is a clear need to develop alternative targeted therapeutics, such as CRISPR-Cas13, which have the ability to be rapidly reprogrammed to target new emerging pandemics.\u201d<\/p>\n While many new treatments for the novel coronavirus are being considered, there is one thing that is certain, Maquat says: \u201cTargeting RNA, or the proteins it produces, is essential for therapeutically combatting this disease.\u201d<\/p>\n Most people living in the United States today have only read about the 1918 flu pandemic and the relatively recent RNA viruses, such as Ebola or Zika, that are seen largely in other countries.<\/p>\n \u201cRNA treatments will most likely be a wave of the future for these and other emerging diseases,\u201d Maquat says. \u201cEpidemiologists know new infectious pathogens are coming given how small the world has become with international travel, including to and from places where humans and animals are in close contact.\u201d<\/p>\n Bats, in particular, are reservoirs for viruses<\/a>. Many bat species are able to live with viruses without experiencing ill effects, given the bats\u2019 unusual physiology. If these bat viruses mutate so they become capable of infecting humans, however, there will be new diseases, Maquat says.<\/p>\n \u201cIt is just a matter of when this will happen and what the virus will be. The hope is that we will be ready and able to develop vaccines against these new viruses with the new pipelines that have been put in place for COVID-19.\u201d<\/p>\n This story was originally published on April 28, 2020, and updated on December 14, 2020.<\/em><\/p>\nWhat does RNA stand for?<\/h2>\n
What is RNA?<\/h2>\n
What does Covid stand for?<\/h2>\n
How does RNA relate to disease?<\/strong><\/h3>\n
How do RNA vaccines work?<\/strong><\/h3>\n
How is Rochester\u2019s RNA research applicable to COVID-19? <\/strong><\/h3>\n
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What role will RNA play in the future of vaccines and disease treatments?<\/strong><\/h3>\n
\nRead more<\/strong><\/h3>\n
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FDA votes to approve emergency use of Pfizer coronavirus vaccine<\/strong><\/a>![\"bat](\"https:\/\/www.rochester.edu\/newscenter\/wp-content\/uploads\/2020\/07\/fea-bats-clues-covid-19.jpg\")
Bats offer clues to treating COVID-19<\/strong><\/a>![\"illustration](\"https:\/\/www.rochester.edu\/newscenter\/wp-content\/uploads\/2020\/07\/2020_july_ace2_gettyimages-1249068502-170667a.jpg\")
Rochester biologists selected for \u2018rapid research\u2019 on COVID-19<\/strong><\/a>