Ljubljana/summary

From 2007.igem.org

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     <dd>-split ubiquitin system
     <dd>-split ubiquitin system
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   <li>Construction of BioBricks for heterodimerization, which represent a powerful platform for engineering cell processes based on protein-protein interactions
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   <li>Construction of <a href="https://2007.igem.org/Ljubljana/biobricks">BioBricks</a> for heterodimerization, which represent a powerful platform for engineering cell processes based on protein-protein interactions
   <li>Introduction of the versatile amplification platform based on the use of T7 RNA polymerase in mammalian cells
   <li>Introduction of the versatile amplification platform based on the use of T7 RNA polymerase in mammalian cells
   <li>Activation device based on the proteolytic cleavage and release of membrane anchored T7 RNA polymerase from the membrane into the cell nucleus
   <li>Activation device based on the proteolytic cleavage and release of membrane anchored T7 RNA polymerase from the membrane into the cell nucleus
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<li>The idea of relying on viral functions could be applied also to other HIV-specific processes (such as genome integration, reverse transcription…)
<li>The idea of relying on viral functions could be applied also to other HIV-specific processes (such as genome integration, reverse transcription…)
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<li>Our system based on BioBricks has been useful for the proof the principle, but for the real application cellular delivery would be much better applied using vectors based on viral delivery
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<li>Our system based on <a href="https://2007.igem.org/Ljubljana/biobricks">BioBricks</a> has been useful for the proof the principle, but for the real application cellular delivery would be much better applied using vectors based on viral delivery
<li>In case of using viral vectors therapy could be delivered specifically to the relevant cells that can be infected by HIV-1 (e.g. similar as T-cell-directed retroviral delivery systems described by David Baltimore at SB2.0)
<li>In case of using viral vectors therapy could be delivered specifically to the relevant cells that can be infected by HIV-1 (e.g. similar as T-cell-directed retroviral delivery systems described by David Baltimore at SB2.0)
<li>Selection of different effectors will (and can) be made based on further experiments – apoptosis can only be used in 100% leak-proof systems, while antiviral and immune response effectors are not as sensitive
<li>Selection of different effectors will (and can) be made based on further experiments – apoptosis can only be used in 100% leak-proof systems, while antiviral and immune response effectors are not as sensitive
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Weakness of all these therapeutics is that they are very sensitive to HIV mutations – HIV can easily mutate and thus become drug resistant. A combination of drugs is used to minimize HIV's potential to develop resistance to each individual drug in the mixture. Some of the drugs induce mutations that have negative effect on the virulence and such drugs can be used in spite of developed resistance.<br><br>
 
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We still do not have a cure for AIDS that would be insensitive to HIV mutations. Our project presents new ways of potential AIDS therapeutics. Our approaches can be considered independent of HIV mutations. We have set up a few of biological ambushes; if HIV manages to avoid them, we presume that it would not be able to infect the cell anyway.</p>
 
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      <h3><span>Classes of Antiretroviral Drugs</span></h3>
 
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      <p class="p1">Antiretroviral drugs are mostly inhibitors of different stages in HIV life cycle. They are targeted at different enzymes or events that are typical for HIV infection – entry of the virus into the cell, reverse transcription, polyprotein cleavage... and are divided into seven main classes (REFERENCA!):<br>
 
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      <h3><span>Development</span></h3>
 
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Revision as of 20:40, 25 October 2007

Company Name

Achievements

  • Design and implementation of three functional systems of activation of anti-HIV defense based on
    -the detection of viral interactions with the cells and
    -cleavage of specific substrate by viral protease
  • Successful detection of CD4-CCR5 heterodimer formation through
    -split tobacco etch virus (TEV) protease
    -split ubiquitin system
  • Construction of BioBricks for heterodimerization, which represent a powerful platform for engineering cell processes based on protein-protein interactions
  • Introduction of the versatile amplification platform based on the use of T7 RNA polymerase in mammalian cells
  • Activation device based on the proteolytic cleavage and release of membrane anchored T7 RNA polymerase from the membrane into the cell nucleus
  • Anchoring of T7 RNA polymerase to the plasma membrane either by
    -fusion to CD4
    -addition of a myristoylation signal
  • Implementation of two different types of effector molecules for
    -induction of cell death (caspase-3)
    -activation of antiviral defense (interferon beta)

Prospects for the future work and real world applications

  • The idea of relying on viral functions could be applied also to other HIV-specific processes (such as genome integration, reverse transcription…)
  • Our system based on BioBricks has been useful for the proof the principle, but for the real application cellular delivery would be much better applied using vectors based on viral delivery
  • In case of using viral vectors therapy could be delivered specifically to the relevant cells that can be infected by HIV-1 (e.g. similar as T-cell-directed retroviral delivery systems described by David Baltimore at SB2.0)
  • Selection of different effectors will (and can) be made based on further experiments – apoptosis can only be used in 100% leak-proof systems, while antiviral and immune response effectors are not as sensitive
  • Similar systems can be prepared for therapy of many other pathogens, particularly viruses (e.g. yellow fiver, SARS, foot and mouth disease…) which contain specific proteases and rely on defined cellular receptors

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