Team:Slovenia/SocietyScientists

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<a style="position:absolute; top:0px; left:490px;" href="https://2012.igem.org/Main_Page"><b>iGEM 2012</b></a>
 
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<li><a href='https://2012.igem.org/Team:Slovenia/TheSwitchDesignedTALregulators'><span>Designed TAL regulators</span></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/TheSwitchDesignedTALregulators'><span>Designed TAL regulators</span></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/TheSwitchMutualRepressorSwitch'><span>Mutual repressor switch</span></a></li>  
<li><a href='https://2012.igem.org/Team:Slovenia/TheSwitchMutualRepressorSwitch'><span>Mutual repressor switch</span></a></li>  
-
<li><a href='https://2012.igem.org/Team:Slovenia/TheSwitchPositiveFeedbackLoopSwitch'><span>Positive feedback loop switch</span></a></li>  
+
<li><a href='https://2012.igem.org/Team:Slovenia/TheSwitchPositiveFeedbackLoopSwitch'><table onclick="window.location = 'https://2012.igem.org/Team:Slovenia/TheSwitchPositiveFeedbackLoopSwitch';" class="newtable"><tr class="newtable"><td class="newtable"><span>Positive feedback loop switch</span></td><td class="newtable"><img style="margin-right:-15px;" width="25px" src="https://static.igem.org/mediawiki/2012/e/ee/Svn12_hp_new.png"></img></td></tr></table></a></li>
 +
    <li><a href='https://2012.igem.org/Team:Slovenia/TheSwitchControls'><table onclick="window.location = 'https://2012.igem.org/Team:Slovenia/TheSwitchControls';" class="newtable"><tr class="newtable"><td class="newtable"><span>Controls</span></td><td class="newtable"><img style="margin-right:-81px;" width="25px" src="https://static.igem.org/mediawiki/2012/e/ee/Svn12_hp_new.png"></img></td></tr></table></a></li>  
  </ul>
  </ul>
</li>
</li>
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<li><a href='https://2012.igem.org/Team:Slovenia/SafetyMechanismsEscapeTag'><span>Escape tag</span></a></li>  
<li><a href='https://2012.igem.org/Team:Slovenia/SafetyMechanismsEscapeTag'><span>Escape tag</span></a></li>  
<li><a href='https://2012.igem.org/Team:Slovenia/SafetyMechanismsTermination'><span>Termination</span></a></li>  
<li><a href='https://2012.igem.org/Team:Slovenia/SafetyMechanismsTermination'><span>Termination</span></a></li>  
-
<li><a href='https://2012.igem.org/Team:Slovenia/SafetyMechanismsMicrocapsuleDegradation'><span>Microcapsule degradation</span></a></li>  
+
    <li><a href="https://2012.igem.org/Team:Slovenia/SafetyMechanismsMicrocapsuleDegradation"><table  onclick="window.location = 'https://2012.igem.org/Team:Slovenia/SafetyMechanismsMicrocapsuleDegradation';" class="newtable"><tr class="newtable"><td class="newtable"><span>Microcapsule degradation</span></td><td class="newtable"><img style="margin-right:-15px;" width="25px" src="https://static.igem.org/mediawiki/2012/e/ee/Svn12_hp_new.png"></img></td></tr></table></a></li>  
  </ul>
  </ul>
</li>
</li>
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<li><a href='https://2012.igem.org/Team:Slovenia/ImplementationHepatitisC'><span>Hepatitis C</span></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/ImplementationHepatitisC'><span>Hepatitis C</span></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/ImplementationIschaemicHeartDisease'><span>Ischaemic heart disease</span></a></li>  
<li><a href='https://2012.igem.org/Team:Slovenia/ImplementationIschaemicHeartDisease'><span>Ischaemic heart disease</span></a></li>  
 +
    <li><a href='https://2012.igem.org/Team:Slovenia/ImplementationImpact'><table onclick="window.location = 'https://2012.igem.org/Team:Slovenia/ImplementationImpact';" class="newtable"><tr class="newtable"><td class="newtable"><span>Impact</span></td><td class="newtable"><img style="margin-right:-86px;" width="25px" src="https://static.igem.org/mediawiki/2012/e/ee/Svn12_hp_new.png"></img></td></tr></table></a></li>
 
 
  </ul>
  </ul>
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  <ul>
  <ul>
<li><a href='https://2012.igem.org/Team:Slovenia/Modeling'><span>Overview</span></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/Modeling'><span>Overview</span></a></li>
-
<li><a href='https://2012.igem.org/Team:Slovenia/ModelingPK'><span>Pharmacokinetics</span></a></li>
+
    <li><a href='https://2012.igem.org/Team:Slovenia/ModelingPK'><table onclick="window.location = 'https://2012.igem.org/Team:Slovenia/ModelingPK';" class="newtable"><tr class="newtable"><td class="newtable"><span>Pharmacokinetics</span></td><td class="newtable"><img style="margin-right:-15px;" width="25px" src="https://static.igem.org/mediawiki/2012/e/ee/Svn12_hp_new.png"></img></td></tr></table></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/ModelingMethods'><span>Modeling methods</span></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/ModelingMethods'><span>Modeling methods</span></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/ModelingMutualRepressorSwitch'><span>Mutual repressor switch</span></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/ModelingMutualRepressorSwitch'><span>Mutual repressor switch</span></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/ModelingPositiveFeedbackLoopSwitch'><span>Positive feedback loop switch</span></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/ModelingPositiveFeedbackLoopSwitch'><span>Positive feedback loop switch</span></a></li>
-
<li><a href='https://2012.igem.org/Team:Slovenia/ModelingQuantitativeModel'><span>Quantitative and stability model</span></a></li>  
+
<li><a href='https://2012.igem.org/Team:Slovenia/ModelingQuantitativeModel'><table onclick="window.location = 'https://2012.igem.org/Team:Slovenia/ModelingQuantitativeModel';" class="newtable"><tr class="newtable"><td class="newtable"><span>Experimental model</span></td><td class="newtable"><img style="margin-right:-15px;" width="25px" src="https://static.igem.org/mediawiki/2012/e/ee/Svn12_hp_new.png"></img></td></tr></table></a></li>  
-
<li><a href='https://2012.igem.org/Team:Slovenia/ModelingInteractiveSimulations'><span>Interactive simulations</span></a></li>
+
    <li><a href='https://2012.igem.org/Team:Slovenia/ModelingInteractiveSimulations'><table onclick="window.location = 'https://2012.igem.org/Team:Slovenia/ModelingInteractiveSimulations';" class="newtable"><tr class="newtable"><td class="newtable"><span>Interactive simulations</span></td><td class="newtable"><img style="margin-right:-15px;" width="25px" src="https://static.igem.org/mediawiki/2012/e/ee/Svn12_hp_new.png"></img></td></tr></table></a></li>
  </ul>
  </ul>
</li>
</li>
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  <ul>
  <ul>
<li><a href='https://2012.igem.org/Team:Slovenia/Notebook'><span>Experimental methods</span></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/Notebook'><span>Experimental methods</span></a></li>
-
<li><a href='https://2012.igem.org/Team:Slovenia/NotebookLablog'><span>Lablog</span></a></li>
+
    <li><a href='https://2012.igem.org/Team:Slovenia/NotebookLablog'><table onclick="window.location = 'https://2012.igem.org/Team:Slovenia/NotebookLablog';" class="newtable"><tr class="newtable"><td class="newtable"><span>Lablog</span></td><td class="newtable"><img style="margin-right:-90px;" width="25px" src="https://static.igem.org/mediawiki/2012/e/ee/Svn12_hp_new.png"></img></td></tr></table></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/NotebookLabSafety'><span>Lab safety</span></a></li>  
<li><a href='https://2012.igem.org/Team:Slovenia/NotebookLabSafety'><span>Lab safety</span></a></li>  
  </ul>
  </ul>
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<li><a href='https://2012.igem.org/Team:Slovenia/Team'><span>Team members</span></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/Team'><span>Team members</span></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/TeamAttributions'><span>Attributions</span></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/TeamAttributions'><span>Attributions</span></a></li>
 +
<li><a href='https://2012.igem.org/Team:Slovenia/TeamCollaborations'><table  onclick="window.location = 'https://2012.igem.org/Team:Slovenia/TeamCollaborations';" class="newtable"><tr class="newtable"><td class="newtable"><span>Collaborations</span></td><td class="newtable"><img style="margin-right:-20px;" width="25px" src="https://static.igem.org/mediawiki/2012/e/ee/Svn12_hp_new.png"></img></td></tr></table></a></li>
<li><a href='https://2012.igem.org/Team:Slovenia/TeamGallery'><span>Gallery</span></a></li>  
<li><a href='https://2012.igem.org/Team:Slovenia/TeamGallery'><span>Gallery</span></a></li>  
<li><a href='https://2012.igem.org/Team:Slovenia/TeamSponsors'><span>Sponsors</span></a></li>  
<li><a href='https://2012.igem.org/Team:Slovenia/TeamSponsors'><span>Sponsors</span></a></li>  
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<h1>Scientists</h1>
<h1>Scientists</h1>
-
<p>Development of new technology also brings the responsibility to consider its potential risks, taking into account also ethical and environmental concerns arising from the rapid progress of synthetic biology. It is also our responsibility to promote the development and public acceptance of synthetic biology, which has potentials to improve the quality of life. </p>
 
-
<p>Among the stakeholders scientists play an important role in the social dimension of our inventions (Figure 1). Scientific assessment of new technology is a very important prerequisite before its translation into tangible applications and dissemination. As the inventors we have to examine the results from the scientific point ourselves but it will also be subjected to the peer review of other scientists, first at the iGEM competition and later in the form of scientific publications, which we expect will follow shortly. </p>
 
-
<img src="X"></img>
 
-
<p><b>Figure 1. Presentation of the results of scientific work.</b> Anže Smole, PhD student from the National Institute of Chemistry, Ljubljana, Slovenia on the meeting "Winter school - Innate Immunity and Synthetic Biology", 21.-23. 3. 2012, Pokljuka, Slovenia. </p>
 
<br/>
<br/>
-
<p>Therefore we are including some thoughts on our project and its continuation and extension. We have already included the discussion on the advantages and drawbacks of microencapsulated cell-based therapy in the section on Implementation. </p>
+
<table class="summary">
-
<p>Results of this project clearly demonstrate the proof of principle of several new ideas, ranging from the foundational advances of designing an almost limitless number of orthogonal switches to the safety mechanisms for therapy based on mammalian cells. Those devices could and should be further tailored for different applications. </p>
+
<tbody class="summary">
-
<p>For the actual therapeutic implementation we would clearly need to prepare a stably transfected cell line with versions of our proposed therapeutic device. Introduction of so many different parts into the genome will be a considerable task. </p>
+
<tr  class="summary">
-
<p>We also pondered on the issue whether we should allow cells to divide inside the microcapsules or to prevent the division, as this may make it more difficult to exactly asses the amount of produced drug and therefore the amount of microcapsules that would need to be implanted. Clearly the use of therapeutics that allow sufficiently broad range of effective therapeutic concentrations would be preferable. For therapy of acute diseases (e.g. a myocardial infarction) where microcapsules would need to perform their task only several weeks it would most likely be sufficient to have a finite amount of stably transfected, nondividing cells within the microcapsule. For this purpose blocking cell cycle might offer an advantage, since the enhanced productivity of cells with a blocked cell cycle has already been reported (Fussenegger et al., 1998). </p>
+
<td  class="summary">
-
<p>In terms of safety mechanisms described within the project, use of pro-drugs to terminate cells seems to be the safest mechanism, although it may be advantageous to select less toxic compound than ganciclovir that have higher therapeutic index and as little as possible effect on host cells. We may have to increase the enzymatic activity for the efficient degradation of microcapsules, although production of alginate lyase may lead to production of antibodies and sensitization of the organism for the repeated exposure. The alternative would be to consider leaving the microcapsules intact, which is currently the case in basically all other applications of microencapsulated cells. </p>
+
<!-- VSEBINA OD TU DALJE -->
-
<p><b>Preclinical studies</b> on animal models will represent the real test of efficiency, long term stability and safety of therapeutic cells. Our <b>pharmacokinetic model</b> will prove as a valuable tool that will allow us to adjust the parameters to improve the model even further and estimate the concentration of therapeutics in different tissues on the basis of the level of therapeutics in the serum. </p>
+
<p>Development of a new technology brings with it the responsibility to consider its potential risks, taking into account the ethical, environmental and other concerns arising from the rapid progress of synthetic biology. It is also our responsibility to promote the development and public acceptance of synthetic biology, which has potentials to improve the quality of life. </p>
-
<p><b>Clinical trials</b> will have to meet all medical, ethical and regulatory requirements. The first clinical trials of applications based on synthetic biology tools are underway (Bugaj and Schaffer, 2012; devices controlling interleukin-12 production for the treatment of cancer). On the 20th of July 2012 the European Medicines Agency’s Committee for Medicinal Products for Human Use has issued a positive opinion that recommends the first gene therapy for approval. These reports encourage and convince us that the realization of clinical potentials of synthetic biology is not so far in the future, but we are aware that the speed of implementing new therapies must be balanced with extreme caution. </p>
+
<p>Among the stakeholders, scientists play an important role in the social dimension of our inventions (Figure 1). Scientific assessment of any new technology is a very important prerequisite before its translation into tangible applications and its dissemination. As the inventors we have to examine the results from the scientific point of view ourselves but it will also be subjected to peer review by other scientists, first at the iGEM competition and later in the form of scientific publications, which we expect will follow shortly. </p>
 +
</p>
 +
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<tbody  class="inliner">
 +
<tr class="inliner"><td class="inliner"><img class="inliner" src="https://static.igem.org/mediawiki/2012/d/d9/Svn12_society_scientists_fig1.jpg"/></td></tr>
 +
<tr class="inliner"><td class="inliner"><b>Figure 1. Presentation of the results of scientific work.</b>  Anže Smole, PhD student from the National Institute of Chemistry, Ljubljana, Slovenia at the meeting "Winter school - Innate Immunity and Synthetic Biology", 21.-23. 3. 2012, Pokljuka, Slovenia.
 +
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 +
</tbody>
 +
</table>
 +
<!-- end figure 1-->
 +
</p>
 +
<p>
 +
 
 +
We therefore include some thoughts on our project and its continuation and extension. We included some discussion
 +
on the advantages and drawbacks of microencapsulated cell-based therapy in the section on <a href="https://2012.igem.org/Team:Slovenia/Implementation">Implementation</a>. </p>
 +
<p>The results of our project clearly demonstrate the proof of principle of several new ideas, ranging from the foundational  
 +
advances of designing an almost limitless number of orthogonal switches to the safety mechanisms for therapy based on mammalian cells.  
 +
Those devices could and should be further tailored for different applications. </p>
 +
<p>For the actual therapeutic implementation we would clearly need to prepare stably transfected cell lines with versions
 +
of our proposed therapeutic device. Introduction of so many different parts into the genome will be a considerable task. </p>
 +
<p>We also pondered on the issue of whether we should allow cells to divide inside the microcapsules or prevent the division,  
 +
as this may make it more difficult to exactly asses the amount of the produced drug and therefore the amount of microcapsules that would need  
 +
to be implanted. Clearly the use of therapeutics that allow sufficiently broad range of effective therapeutic concentrations would be  
 +
preferable. For therapy of acute diseases (e.g. myocardial infarction) where microcapsules would need to perform their task only for several
 +
weeks it would most likely be sufficient to have a finite amount of stably transfected, nondividing cells within the microcapsule.  
 +
For this purpose, blocking the cell cycle might offer an advantage, since the enhanced productivity of cells with a blocked cell cycle has  
 +
already been reported (Fussenegger et al., 1998). </p>
 +
<p>In terms of safety mechanisms described within the project, use of prodrugs to terminate cells seems to be the safest mechanism,
 +
although it may be advantageous to select compounds less toxic than ganciclovir that have a higher therapeutic index and have as little as possible effect on host cells. We may have to increase the enzymatic activity of alginate lyase for the efficient degradation of microcapsules, although production of alginate lyase may lead to production of antibodies and a sensitization of the organism to a repeated exposure. The alternative would be to consider leaving the microcapsules intact, which is currently the case in all other applications of microencapsulated cells. </p>
 +
<p><b>Preclinical studies</b> on animal models will represent the real test of efficiency, long term stability and safety of therapeutic
 +
cells. Our <b>pharmacokinetic model</b> should prove as a valuable tool that will allow us to adjust the parameters to improve the model  
 +
even further and estimate the concentration of therapeutics in different tissues based on the level of therapeutics in the serum. </p>
 +
<p><b>Clinical trials</b> will have to meet all medical, ethical and regulatory requirements. The first clinical trials of applications  
 +
based on synthetic biology tools are already underway (Bugaj and Schaffer, 2012; devices controlling interleukin-12 production for the treatment
 +
of cancer). On the 20th of July 2012 the European Medicines Agency’s Committee for Medicinal Products for Human Use has issued a positive
 +
opinion that recommends the first gene therapy for approval. These reports encourage and convince us that the realization of clinical
 +
potentials of synthetic biology is not so far in the future, but we are aware that the speed of implementing new therapies must be determined by elimination of all safety concerns. </p>
<h2 style="color:grey;">References</h2>
<h2 style="color:grey;">References</h2>
<p style="color:grey;">
<p style="color:grey;">
-
Bugaj, L.J., and Schaffer, D.V. (2012) Bringing next-generation therapeutics to the clinic through synthetic biology. <i> Curr. Opin. Chem. Biol. </i> <b>16</b>, 355-361.<br/><br/></p>
+
Bugaj, L.J., and Schaffer, D.V. (2012) Bringing next-generation therapeutics to the clinic through synthetic biology. <i> Curr. Opin. Chem. Biol. </i> <b>16</b>, 355-361.<br/><br/>
-
<p style="color:grey;">
+
Fussenegger, M., Schlatter, S., Dätwyler, D., Mazur, X. and Bailey, J.E. (1998) Controlled proliferation by multigene metabolic engineering enhances the productivity of Chinese hamster ovary cells. <i> Nat. Biotechnol. </i> <b>16</b>, 468-72.
-
Fussenegger, M., Schlatter, S., Dätwyler, D., Mazur, X. and Bailey, J.E. (1998) Controlled proliferation by multigene metabolic engineering enhances the productivity of Chinese hamster ovary cells. <i> Nat. Biotechnol. </i> <b>16</b>, 468-72.<br/><br/></p>
+
 
 +
<div style="clear:both;"></div>
 +
 
 +
 
 +
 
 +
<hr>
 +
<b>
 +
Next: <a href='https://2012.igem.org/Team:Slovenia/SocietyMedicalDoctors'>Physicians >></a>
 +
</b>
<!-- KONEC VSEBINE -->
<!-- KONEC VSEBINE -->

Latest revision as of 20:51, 26 October 2012


Scientists


Development of a new technology brings with it the responsibility to consider its potential risks, taking into account the ethical, environmental and other concerns arising from the rapid progress of synthetic biology. It is also our responsibility to promote the development and public acceptance of synthetic biology, which has potentials to improve the quality of life.

Among the stakeholders, scientists play an important role in the social dimension of our inventions (Figure 1). Scientific assessment of any new technology is a very important prerequisite before its translation into tangible applications and its dissemination. As the inventors we have to examine the results from the scientific point of view ourselves but it will also be subjected to peer review by other scientists, first at the iGEM competition and later in the form of scientific publications, which we expect will follow shortly.

Figure 1. Presentation of the results of scientific work. Anže Smole, PhD student from the National Institute of Chemistry, Ljubljana, Slovenia at the meeting "Winter school - Innate Immunity and Synthetic Biology", 21.-23. 3. 2012, Pokljuka, Slovenia.

We therefore include some thoughts on our project and its continuation and extension. We included some discussion on the advantages and drawbacks of microencapsulated cell-based therapy in the section on Implementation.

The results of our project clearly demonstrate the proof of principle of several new ideas, ranging from the foundational advances of designing an almost limitless number of orthogonal switches to the safety mechanisms for therapy based on mammalian cells. Those devices could and should be further tailored for different applications.

For the actual therapeutic implementation we would clearly need to prepare stably transfected cell lines with versions of our proposed therapeutic device. Introduction of so many different parts into the genome will be a considerable task.

We also pondered on the issue of whether we should allow cells to divide inside the microcapsules or prevent the division, as this may make it more difficult to exactly asses the amount of the produced drug and therefore the amount of microcapsules that would need to be implanted. Clearly the use of therapeutics that allow sufficiently broad range of effective therapeutic concentrations would be preferable. For therapy of acute diseases (e.g. myocardial infarction) where microcapsules would need to perform their task only for several weeks it would most likely be sufficient to have a finite amount of stably transfected, nondividing cells within the microcapsule. For this purpose, blocking the cell cycle might offer an advantage, since the enhanced productivity of cells with a blocked cell cycle has already been reported (Fussenegger et al., 1998).

In terms of safety mechanisms described within the project, use of prodrugs to terminate cells seems to be the safest mechanism, although it may be advantageous to select compounds less toxic than ganciclovir that have a higher therapeutic index and have as little as possible effect on host cells. We may have to increase the enzymatic activity of alginate lyase for the efficient degradation of microcapsules, although production of alginate lyase may lead to production of antibodies and a sensitization of the organism to a repeated exposure. The alternative would be to consider leaving the microcapsules intact, which is currently the case in all other applications of microencapsulated cells.

Preclinical studies on animal models will represent the real test of efficiency, long term stability and safety of therapeutic cells. Our pharmacokinetic model should prove as a valuable tool that will allow us to adjust the parameters to improve the model even further and estimate the concentration of therapeutics in different tissues based on the level of therapeutics in the serum.

Clinical trials will have to meet all medical, ethical and regulatory requirements. The first clinical trials of applications based on synthetic biology tools are already underway (Bugaj and Schaffer, 2012; devices controlling interleukin-12 production for the treatment of cancer). On the 20th of July 2012 the European Medicines Agency’s Committee for Medicinal Products for Human Use has issued a positive opinion that recommends the first gene therapy for approval. These reports encourage and convince us that the realization of clinical potentials of synthetic biology is not so far in the future, but we are aware that the speed of implementing new therapies must be determined by elimination of all safety concerns.

References

Bugaj, L.J., and Schaffer, D.V. (2012) Bringing next-generation therapeutics to the clinic through synthetic biology. Curr. Opin. Chem. Biol. 16, 355-361.

Fussenegger, M., Schlatter, S., Dätwyler, D., Mazur, X. and Bailey, J.E. (1998) Controlled proliferation by multigene metabolic engineering enhances the productivity of Chinese hamster ovary cells. Nat. Biotechnol. 16, 468-72.


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