ERC

The ERC Advanced Grant funding is amongst the most prestigious and competitive EU funding schemes, providing researchers with the opportunity to pursue ambitious, curiosity-driven projects that could lead to major scientific breakthroughs. They are awarded to established, leading researchers with a proven track-record of significant research achievements over the past decade. Professor Kenneth Dawson, Director of the CBNI grouping , Chair of Physical Chemistry and Full Professor at UCD School of Chemistry, has been awarded an ERC Advanced Grant for his projectFunctionalNanoTher.

The Project: FunctionalNanoTher

Professor Dawson’s lab at CBNI has shown that key naturally occurring (endogenous) nanosized assemblies pass important messages between systems and organs within the body. New techniques have allowed them to isolate and study these signals and reveal that in stark distinction to the man-made nanostructured therapeutic structures currently studied and applied, these structures are actively ‘recognised’ and interpreted by cells and tissue, and thereby granted access to most protected biological niches. Differing from well-known isolated biomolecular ligand-receptor type interactions, such interactions constitute a remarkable defensive gating mechanism that prevents nearly all nanostructures from gaining substantive biological access, that is the reason it has been so difficult to target nanoscale therapies. So far, with just marginal access, there has been striking successes with recent mRNA vaccines.
Over some years our research had progressively led us to conclude that certain key naturally occurring (endogenous) nanosized assemblies passed around key messages between systems and organs within the body. However, the challenge had long been that the body has so many such nanosized biological structures (a few key ones, some others with limited meaning, some merely carriers of waste) that it was hard to isolate, interpret and understand these signals against the ‘background chatter’. However, new techniques allowed such natural structures to be removed from the background, and studied in sufficient amounts to understand first how they are built and then watch how they are processed and interpreted in cells. In stark distinction to the man-made nanostructured therapeutic structures currently studied and applied, we realized that these structures are actively ‘recognized’ and interpreted by cells and tissue, and thereby granted access to most protected biological niches. The mechanisms of biological recognition and interpretation of complex nanostructures are still being unravelled, but after some years we now know quite a lot about them-sufficient to appreciate that they are quite different from well-known isolated biomolecular ligand-receptor type interactions. For example, such recognition interactions constitute a remarkable defensive gating mechanism that prevents nearly all nanostructures from gaining substantive biological access, and that is the reason it has been so difficult to target nanoscale therapies in the past. So far, we have only been granted marginal access, and while that limited access has had striking successes such as in recent mRNA vaccines, the story has just begun.Now that we can see the bodies’ own natural messaging systems at work, we are able to study them in depth.  

The ERC Advanced Grant funded FunctionalNanoTher will now analyse such defence mechanisms in depth and build structured RNA (and other) therapies that can leverage the endogenous nanoscale communications pathways. Early results suggest that tapping into this network will radically change how we think about nanoscale therapies, leading to much more efficient vaccines, and allowing for placement of sufficient amounts of co-ordinated therapeutic compounds into key disease targets, allowing them to cooperate in situ. These tiny amounts of therapeutic material will work alongside and leverage the body’s own nanoscale trafficking and communications systems, co-operating with them rather than trying to break out or avoid them. This presents an opportunity to re-examine challenging targets such as the tumour microenvironment, from the point of view of complete re-engineering and rewiring, rather than only killing some of its cells within it or activating coupled immune systems.

This novel approach will enable significant advances in therapeutic efficacy against a much wider range of disease targets. Crucially, it will allow for a new level of safe operation and greatly limit side effects associated with such therapies.