Team:Freiburg Bioware/Safety
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<span style="color:DarkGreen"><b>Which specific biosafety rules or guidelines do you have to consider in your country?</b></span> | <span style="color:DarkGreen"><b>Which specific biosafety rules or guidelines do you have to consider in your country?</b></span> | ||
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<p> | <p> | ||
In Germany all working that includes recombinant DNA technologies is regulated by the <a href=http://bundesrecht.juris.de/gentg/index.html>Gesetz zur Regelung der Gentechnik</a>. This law regulates general aspects arising from the life sciences and refers for more precise interpretations in §4 to the <a href=http://bundesrecht.juris.de/gentg/__4.html>Zentrale Kommission für die Biologische Sicherheit</a>. The ZKBS is a commission composed of 20 technical experts that releases yearly statements to actual issues of biosafety. So far the ZKBS released three stratements affecting the work with Adeno-associated viral systems | In Germany all working that includes recombinant DNA technologies is regulated by the <a href=http://bundesrecht.juris.de/gentg/index.html>Gesetz zur Regelung der Gentechnik</a>. This law regulates general aspects arising from the life sciences and refers for more precise interpretations in §4 to the <a href=http://bundesrecht.juris.de/gentg/__4.html>Zentrale Kommission für die Biologische Sicherheit</a>. The ZKBS is a commission composed of 20 technical experts that releases yearly statements to actual issues of biosafety. So far the ZKBS released three stratements affecting the work with Adeno-associated viral systems | ||
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<a href=https://static.igem.org/mediawiki/2010/a/ae/Freiburg10_Advises_for_AAV_carrying_cell_cycle_regulating_genes_2004.pdf><sup>27,</sup></a> | <a href=https://static.igem.org/mediawiki/2010/a/ae/Freiburg10_Advises_for_AAV_carrying_cell_cycle_regulating_genes_2004.pdf><sup>27,</sup></a> | ||
<a href=https://static.igem.org/mediawiki/2010/d/dd/Freiburg10_Risk_assessment_of_human_Adeno-associated_viruses_and_AAV_derived_vectors_2005.pdf><sup>28</sup></a>. These documents were used to assess the dangers that could arise from our project to team members and the enviroment. | <a href=https://static.igem.org/mediawiki/2010/d/dd/Freiburg10_Risk_assessment_of_human_Adeno-associated_viruses_and_AAV_derived_vectors_2005.pdf><sup>28</sup></a>. These documents were used to assess the dangers that could arise from our project to team members and the enviroment. | ||
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</p><br><br> | </p><br><br> | ||
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At the Albert-Ludwigs-University Freiburg for all concerns of security the <a href=http://www.sicherheit.uni-freiburg.de>Stabsstelle Sicherheit</a> is responsible and to contact if questions arise. Especially for questions of biological security Dr. Petra Markmeyer-Pieles is cognizant. We contacted her a first time befor the begin of our project in March when it was clear that the Adeno-associated Virus (AAV-2) was chosen as the topic of our project. At that time she proposed to do the cloning in the AAV-2 that is for sure to handle under biological security level 1 and to prepare everything for work under biological security level 2 to satisfy the precaution principle. | At the Albert-Ludwigs-University Freiburg for all concerns of security the <a href=http://www.sicherheit.uni-freiburg.de>Stabsstelle Sicherheit</a> is responsible and to contact if questions arise. Especially for questions of biological security Dr. Petra Markmeyer-Pieles is cognizant. We contacted her a first time befor the begin of our project in March when it was clear that the Adeno-associated Virus (AAV-2) was chosen as the topic of our project. At that time she proposed to do the cloning in the AAV-2 that is for sure to handle under biological security level 1 and to prepare everything for work under biological security level 2 to satisfy the precaution principle. | ||
The precaution principle was realized and all viral vectors that contained a modified capsid were handled under SII conditions until proven harmless. | The precaution principle was realized and all viral vectors that contained a modified capsid were handled under SII conditions until proven harmless. | ||
- | In August the planing of the project was completed, summarized in an <a href=https://static.igem.org/mediawiki/2010/7/76/Freiburg10_Safetyapplication.pdf>Biosafety application<sup>30</sup></a> and handed to the department for biological security who approve the application in an <a href=https://static.igem.org/mediawiki/2010/1/18/Freiburg10_Safetyconfirmation.jpg>official BSL1 confirmation<sup>31</sup></a>official BSL1 confirmation for our project.</p> | + | In August the planing of the project was completed, summarized in an <a href=https://static.igem.org/mediawiki/2010/7/76/Freiburg10_Safetyapplication.pdf>Biosafety application<sup>30</sup></a> and handed to the department for biological security who approve the application in an <a href=https://static.igem.org/mediawiki/2010/1/18/Freiburg10_Safetyconfirmation.jpg>official BSL1 confirmation<sup>31</sup></a>official BSL1 confirmation for our project.</p><br><br> |
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The requirements for the physical containment were fullfilled by performing all manipulation on the AAV in an BSL II laboratory that guaranted a restriction of persons that entered the laboratory.</li> | The requirements for the physical containment were fullfilled by performing all manipulation on the AAV in an BSL II laboratory that guaranted a restriction of persons that entered the laboratory.</li> | ||
<li><b>6) Hazard minimization</b> | <li><b>6) Hazard minimization</b> | ||
- | For the AAV-2 there are no sugestive activitis because the possible danger that runs out of the AAV is comparably low, vaccination is not avilible and biomonitoring is not necessary.</li></p> | + | For the AAV-2 there are no sugestive activitis because the possible danger that runs out of the AAV is comparably low, vaccination is not avilible and biomonitoring is not necessary.</li></p><br><br> |
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For this reason we estimate the risk of a accidental transformation of <a href=https://static.igem.org/mediawiki/2010/e/e0/Freiburg10_AAv293_cell_line.pdf>AAV-293</a> cells with all three plasmids for negligible. | For this reason we estimate the risk of a accidental transformation of <a href=https://static.igem.org/mediawiki/2010/e/e0/Freiburg10_AAv293_cell_line.pdf>AAV-293</a> cells with all three plasmids for negligible. | ||
Nevertheless we considered it useful to mark every BioBrick or Composite Part in the Registry that contributes to the production or is capable of producing viral vectors when transformed under the previously mentioned conditions. | Nevertheless we considered it useful to mark every BioBrick or Composite Part in the Registry that contributes to the production or is capable of producing viral vectors when transformed under the previously mentioned conditions. | ||
- | </p> | + | </p><br><br> |
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<blockquote>Every grout has a set of norms: a code of conduct about what is acceptable beahviour (Jaques, 2004]<a href=http://www.ncbi.nlm.nih.gov/pubmed/16819452> <sup>19</sup></a></blockquote> | <blockquote>Every grout has a set of norms: a code of conduct about what is acceptable beahviour (Jaques, 2004]<a href=http://www.ncbi.nlm.nih.gov/pubmed/16819452> <sup>19</sup></a></blockquote> | ||
+ | </p><br><br> | ||
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Additional to this secure working environment the system itself can be optimized according to biosafety aspects, means to reduce it's viability outside the laboratory. This aim can be approached by reducing the systems ability to evolve, proliferate and interact with it's environment. A common method to achieve this goal is to engineer microorganisms in a way that they depend on nutrients that can't be found in the environment in sufficient amount. | Additional to this secure working environment the system itself can be optimized according to biosafety aspects, means to reduce it's viability outside the laboratory. This aim can be approached by reducing the systems ability to evolve, proliferate and interact with it's environment. A common method to achieve this goal is to engineer microorganisms in a way that they depend on nutrients that can't be found in the environment in sufficient amount. | ||
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For sure there is allway the possibility that knowledge to produce transgene viral vectors could be used to produce bioweapons. Therefor it was important for us to use a system that does not bear the risk that someone could use it for evil purpose. In the case of the Adeno-associated virus the very limited packaging capacity is the major reason that excludes it from the list of agents that could realistically be used for the pruduction of bioweapons. Even a fully replication potent AAV will depend on the coninfection of a helpervirus and is therefore not suitable for a fast propagation in an population. | For sure there is allway the possibility that knowledge to produce transgene viral vectors could be used to produce bioweapons. Therefor it was important for us to use a system that does not bear the risk that someone could use it for evil purpose. In the case of the Adeno-associated virus the very limited packaging capacity is the major reason that excludes it from the list of agents that could realistically be used for the pruduction of bioweapons. Even a fully replication potent AAV will depend on the coninfection of a helpervirus and is therefore not suitable for a fast propagation in an population. | ||
Additional to this point we concentrated our project on the retargeting of the virus - means to make the broad tropismn more narrow and to decrease the transduction efficiency in the most cases. This modification is usually mainly required for medical purposes. Also we did neither investigate possibilities to shield the vector from the immune system of potential host nor ways to bypass an existing immunity. | Additional to this point we concentrated our project on the retargeting of the virus - means to make the broad tropismn more narrow and to decrease the transduction efficiency in the most cases. This modification is usually mainly required for medical purposes. Also we did neither investigate possibilities to shield the vector from the immune system of potential host nor ways to bypass an existing immunity. | ||
- | </p> | + | </p><br><br> |
Revision as of 00:53, 23 October 2010
Biosafety
Legal regularisation in the Federal Republic of Germany
In Germany all working that includes recombinant DNA technologies is regulated by the Gesetz zur Regelung der Gentechnik. This law regulates general aspects arising from the life sciences and refers for more precise interpretations in §4 to the Zentrale Kommission für die Biologische Sicherheit. The ZKBS is a commission composed of 20 technical experts that releases yearly statements to actual issues of biosafety. So far the ZKBS released three stratements affecting the work with Adeno-associated viral systems 26, 27, 28. These documents were used to assess the dangers that could arise from our project to team members and the enviroment.
At the Albert-Ludwigs-University Freiburg for all concerns of security the Stabsstelle Sicherheit is responsible and to contact if questions arise. Especially for questions of biological security Dr. Petra Markmeyer-Pieles is cognizant. We contacted her a first time befor the begin of our project in March when it was clear that the Adeno-associated Virus (AAV-2) was chosen as the topic of our project. At that time she proposed to do the cloning in the AAV-2 that is for sure to handle under biological security level 1 and to prepare everything for work under biological security level 2 to satisfy the precaution principle. The precaution principle was realized and all viral vectors that contained a modified capsid were handled under SII conditions until proven harmless. In August the planing of the project was completed, summarized in an Biosafety application30 and handed to the department for biological security who approve the application in an official BSL1 confirmation31official BSL1 confirmation for our project.
Our project was designed in a way that it avoids any serious safety issues as far as possible. When working with infectious particles a minimal risk for the researcher is allways present. This risk was minimized by restricting the transduced genes to fluorescent proteins and prodrug convertases that are already proven not to harm human cells in the absece of the corresponding prodrug. A potential danger for the public or the environment was minimized as much as possible by following strictly the rules of Good Laboratory Practice (GLP) and the abdication of using randomized insertions in the capsid and of replication potent viruses. Minimizing the risk for team members and the society was was allways one of the major concerns, especially because worries about undergraduate students manipulating a virus could arise. The security concept will be explained by quoting and explaining the six guiding principles for safe manipulation of Gene Manipulated Organisms (GMOs) as summarized in Kimman et al. ; 200818.
Several composite parts that were assembled by our Team this year are alone capable of producing infectious viral particles when transduced together with a vector plasmid and a helper plasmid into AAV-293 cells. These special cells provide the adenoviral gene E1 stabily integrated in trans. These cells are not provided in the Virus Construction Kit nor availible in the Parts Registry and have to purchased from other laboratories or a commercial supplyer. For this reason we estimate the risk of a accidental transformation of AAV-293 cells with all three plasmids for negligible. Nevertheless we considered it useful to mark every BioBrick or Composite Part in the Registry that contributes to the production or is capable of producing viral vectors when transformed under the previously mentioned conditions.
psychological research into the concept of "identity-driven decision-making" (Torpman,2004) 19
Every grout has a set of norms: a code of conduct about what is acceptable beahviour (Jaques, 2004] 19
Trade-off between potential misuse and promising medical progress - The Adeno-associated Virus as an example
In principle each research-project that bears any risks for engaged researchers, mankind or the environment should be treated under the precautionary principle as proposed 11: "treat synthetic microorganisms as dangerous until proven harmless".
This would mean to work on such synthetic DNA containing Bio Bricks at least under Biological security levels two.
Additional to this secure working environment the system itself can be optimized according to biosafety aspects, means to reduce it's viability outside the laboratory. This aim can be approached by reducing the systems ability to evolve, proliferate and interact with it's environment. A common method to achieve this goal is to engineer microorganisms in a way that they depend on nutrients that can't be found in the environment in sufficient amount.
Biosecurity
For sure there is allway the possibility that knowledge to produce transgene viral vectors could be used to produce bioweapons. Therefor it was important for us to use a system that does not bear the risk that someone could use it for evil purpose. In the case of the Adeno-associated virus the very limited packaging capacity is the major reason that excludes it from the list of agents that could realistically be used for the pruduction of bioweapons. Even a fully replication potent AAV will depend on the coninfection of a helpervirus and is therefore not suitable for a fast propagation in an population. Additional to this point we concentrated our project on the retargeting of the virus - means to make the broad tropismn more narrow and to decrease the transduction efficiency in the most cases. This modification is usually mainly required for medical purposes. Also we did neither investigate possibilities to shield the vector from the immune system of potential host nor ways to bypass an existing immunity.
used