Team:Warwick

From 2014.igem.org

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             <p> NB. This is the home page, which will serve as the splash screen once we get that working. The splash screen is sort of the entry portal, which will have our logo and 'Replicon' title (w/ tagline), and some kind of sexy background, and from where users will click through the power button to enter the website.
             <p> NB. This is the home page, which will serve as the splash screen once we get that working. The splash screen is sort of the entry portal, which will have our logo and 'Replicon' title (w/ tagline), and some kind of sexy background, and from where users will click through the power button to enter the website.
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<p>  <h2> What is a replicon? </h2> <br> <br> <p></p><p></p>
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Revision as of 13:41, 2 September 2014

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Gene therapy has been long sought after in biology. Its applications are extremely wide ranging, as by manipulating the genome a cell, you can in theory completely manipulate a cell to make it do whatever you want. This is essentially the same goal as synthetic biology, however the key difference is that gene therapy focuses on modifying the genes of cells in animals that have already grown beyond embryonic stage, rather than individual cells on their own. There are many problems with current gene therapy, including it being dangerous, being extremely difficult to perform, its possibility of modifying the DNA of cells in ways that can't be predicted, or the gene therapy not being permanent. Our project is to try and solve some of these problems by using a type of RNA called a 'replicon'.

What is a replicon?



A replicon is RNA that acts to replicate itself on its own using only the ribozymes of the cell. RNA usually degrades very quickly in cells, but a replicon should last permanently, because it should replicate faster than it can be degraded. Several viruses use replicons as their method of manipulating cells. Our idea is to take parts from the genome of hepatitis C (HCV) and modify it so that instead of doing damage to the body, it 'silences' harmful genes. To do this, we want to add an siRNA sequence to a replicon sequence. siRNA (small interfering RNA) is RNA that contains part of a complimentary nucleotide sequence to a particular RNA sequence. The human cell breaks this sequence down, and then continues to break down complimentary RNA sequences to this, including the sequence we want to target.

What are the advantages of this over conventional gene therapy?



Nowhere in this process is the actual DNA of the cell modified, so this removes the danger of DNA of the cell being modified in a way that is unwanted. This also improves upon conventional gene silencing, which involves siRNA only, as the replicon represents a permanent source of siRNA, greatly increasing the efficiency of the gene silencing. Our proposed method of delivery is to use a viral vector, technology which unfortunately doesn't exist yet, but could be developed within the next few decades. This method would allow for gene silencing in multicellular organisms, the holy grail of gene therapy.

Our motivation



  • Diabetes The majority of our siRNA testing will revolve around inhibiting Dipeptidyl peptidase IV (DPP-IV). DPP-IV causes increased speed of degradation of incretins, which when undegraded increase the duration of production of insulin. If our system works, it could act as a long-term treatment for type II diabetes as the treatment. Current DPP-IV inhibitors are very expensive at $885 for 90 tabs, four of which must be taken each day These act non-specifically causing side effects such as headaches, nausea and gastrointestinal issues. DPP-IV also acts as a tumour suppressor so administering these non specifically means tumour risk is increased throughout the body. Our system enables administration to specific cell types using a programmed viral vector and can be destroyed using an exogenous compound in the event of tumour formation. The administration of this would be very infrequent due to the self-replicating characteristic of the RNA strand and could improve patient compliance and quality of life.
  • Ebola Ebola has recently come to the headlines due to the epidemic currently occurring in Central Africa. Due to its initial appearance in a township the infectivity has been revealed to be much higher than initially suspected and is spreading devastatingly through multiple countries. The most effective treatment to date is re-hydration, reducing the mortality rate to 50% and ZMAPP, a combination of three humanised, monoclonal antibodies produced by genetic engineering targeting a specific gene of the Zaire ebolavirus aiding the immune system in combating the disease. Unfortunately the world reserves were exhausted at the end of September and research into other treatments has been undertaken. There looks to be significant promise in the use of siRNAs, such as TKM-Ebola, this interferes with the replication of the Ebola virus at an RNA level and has been shown to give 100% protection in macaques from lethal doses of Zaire ebolavirus. Our system could be adapted to deliver the siRNA against Ebola and could act as a prophylactic or poat infection treatment during an outbreak.
  • Alzheimer's
  • liver cancer
  • First paragraph goes here. Check out this list of HTML tags, or "elements", for help writing up your material in the desired fashion.

    It can be easier to use a text editor like Sublime Text (with the HTML syntax) to write this up. Alternatively, for some more nuanced tips, learn about Dave Matthews and his fabulous medicinal properties.

    NB. This is the home page, which will serve as the splash screen once we get that working. The splash screen is sort of the entry portal, which will have our logo and 'Replicon' title (w/ tagline), and some kind of sexy background, and from where users will click through the power button to enter the website.