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Logical re-routing of cellular communication networks by DNA origami nanorobot

Final Report Summary - DNA NANO-ROUTERS (Logical re-routing of cellular communication networks by DNA origami nanorobot)

The long-term goal of project NANOROUTERS has been to design nanoscale robots, fabricated from synthetic DNA molecules, capable of re-routing cellular communication between cells; and to demonstrate these in a clinically-relevant model. Communication between cells is a crucial aspect of most human diseases, including cancer, autoimmune diseases, transplant rejection, and more. The ability to hijack and manipulate this communication at the organism scale could open a novel strategy for controlling and abrogating these diseases.
The work carried out in the project focused on the design of DNA robots which can be synthesised in large scale, made entirely of DNA (and not include chemical drugs and proteins, to maintain material homogeneity and manufacturing simplicity); their demonstration in multiple-cell-type systems in vitro, and finally demonstration in an organ-on-chip system, by the end of 2017.
Our results indicate several profound findings. First, in simple systems where two cell types, A and B, are communicating in order to maintain their activity (which, in-vivo, could translate into a disease state), it is possible to hijack a single signalling factor or more than one, using DNA robots. These findings enabled the precise calculation of robot-to-signal ratio required to assume full control over the entire signal traffic between the cells. Second, cellular activity can be controlled by this action. Third, a signal can be even re-routed back to the same cell, or simply captured without delivery to any destination, effectively eliminating it from the system. These results were recapitulated in more complex systems, up to 4 cell types. Finally, we demonstrated this concept on an organ-on-chip system, that mimics human bone marrow (as described in Nature Methods vol. 11 no. 6, 2014), with results to be implemented in a mouse model in the following weeks.
Thanks to the funding awarded to this project, the work has achieved its goals in full, with exciting results ready for implementation in rodent models in mid-2018, and publication thereafter.