Final Report Summary - IMEDGEN (Intracellular Methylases Delivery as therapeutic tool for carcinoma specific regulation of Gene expression)
The goal of the IMEDGEN consortium was the generation of a prototype of a new generation of drugs, which are based on the combination of established technologies in the field of protein engineering, DNA-targeting and drug delivery.
The project has shown that the objective to delivery M.Sss1 to silence DNA expression is possible. The delivery of proteins towards a cell is at this moment a rapid progressing future in the research community. However, the goal of our project to generate a double targeted magic bullit has not been published or presented in abstract or lecture as far as know to us.
At BRC Szeged we have generated a mutant for M.Sss1 C141S which shows only very little rest activity. RWTH Aachen has been able to couple a TFO to this enzyme. At Synvolux we were able to enwrap the protein in such a way the GUMC could deliver it to cells. And Epigenomics was able to detect methylation in the DNA of these cells by Bisulphite sequencing.
A major achievement at RWTH Aachen was the manufacturing of a highly specific M.SssI-TFO conjugate using a C141S mutant which shows only very little rest activity. RWTH Aachen has proven that in vitro this conjugate only shows methylation activity at the CpG site next to the TFO binding. Because the TFO binding site is located at the EpCAM promoter region, it is expected that this specific methylation will result in a knock down of the EpCAM expression. At Synvolux we were able to produce targeted delivery to a specific cell type, by targeting a specific surface marker.
The final step, that is the delivery of the highly specific M.SssI-TFO conjugate in vivo, could not be completed yet, due to lack of time. However, this experiment will be conducted in the near future.
Dissemination efforts have been made by several company visits and fair attendances. As a result of these discussions we concluded that there is a pharmaceutical interest for the approach developed by the consortium, however pharmaceutical industries encouraged us to proceed and to re-inform them at the moment we have reached the proof of principle in animals.
More than 90 % of the deliverables of the project were reached and the results have shown how powerful this technology can be that the company of the coordinator has decided to continue with the project to generate the POP in animals within the next year. Synvolux therapeutics is confident that this POP will be an excellent basis for the further dissemination and use of the product concept which has been developed.
The project has shown that the objective to delivery M.Sss1 to silence DNA expression is possible. The delivery of proteins towards a cell is at this moment a rapid progressing future in the research community. However, the goal of our project to generate a double targeted magic bullit has not been published or presented in abstract or lecture as far as know to us.
At BRC Szeged we have generated a mutant for M.Sss1 C141S which shows only very little rest activity. RWTH Aachen has been able to couple a TFO to this enzyme. At Synvolux we were able to enwrap the protein in such a way the GUMC could deliver it to cells. And Epigenomics was able to detect methylation in the DNA of these cells by Bisulphite sequencing.
A major achievement at RWTH Aachen was the manufacturing of a highly specific M.SssI-TFO conjugate using a C141S mutant which shows only very little rest activity. RWTH Aachen has proven that in vitro this conjugate only shows methylation activity at the CpG site next to the TFO binding. Because the TFO binding site is located at the EpCAM promoter region, it is expected that this specific methylation will result in a knock down of the EpCAM expression. At Synvolux we were able to produce targeted delivery to a specific cell type, by targeting a specific surface marker.
The final step, that is the delivery of the highly specific M.SssI-TFO conjugate in vivo, could not be completed yet, due to lack of time. However, this experiment will be conducted in the near future.
Dissemination efforts have been made by several company visits and fair attendances. As a result of these discussions we concluded that there is a pharmaceutical interest for the approach developed by the consortium, however pharmaceutical industries encouraged us to proceed and to re-inform them at the moment we have reached the proof of principle in animals.
More than 90 % of the deliverables of the project were reached and the results have shown how powerful this technology can be that the company of the coordinator has decided to continue with the project to generate the POP in animals within the next year. Synvolux therapeutics is confident that this POP will be an excellent basis for the further dissemination and use of the product concept which has been developed.