DNA NANO-ROUTERS · Logical re-routing of cellular communication networks by DNA origami nanorobot
FP7 — People (Marie Curie Actions)
- Duration
- 2013-12-01 → 2017-11-30
- EU contribution
- €100,000
- Participants
- 2
- Scheme
- MC-CIG
Lines connect the coordinator with its partners.
Results in brief
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.
Data: CORDIS, © European Union
Project objective
Almost every aspect of higher organism biology such as metabolism, growth and immunity, is regulated by intricate communication networks between multiple cell types. The ability to skew or interfere with these networks could lead to new ways to alleviate diseases caused or maintained by the interacting cells. However, since these cells are often dispersed across the entire organism, precise modulation of a single communication line is very challenging. In this project I propose to achieve this goal by DNA origami nanorobots programmed as routing devices for cell-cell communication. Each nanorobot is programmed to collect and sequester a specific type of signal molecule (cytokine, hormone etc.), and deliver it exclusively to a specific type of cell. Once programmed, a large group of nanorobots (~1016) effectively controls the traffic of signal molecules within an entire network, rendering it susceptible to arbitrary manipulations. These include re-routing signals to different cell addresses, up- or down-tuning the traffic volume in the path, or preventing a specific cell type from transmitting and receiving signals. This technology presents an advanced working draft towards automated biology as a strategy to solve challenges such as food, sustainable energy, emerging diseases etc.
Original text from CORDIS.
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Data: CORDIS, © European Union