Functional Nanoscale Therapeutics

Introduction

We will develop new functional nanoscale medicines that engage and co-operate with cellular pathways designed to process and extract useful information from endogenous nanostructures, as well as protect the organism from nanoscale pathogens.

Functional Hybrid Nanostructures

We show how functional hybrid nanostructures, part-synthetic and part-cell-derived biomolecular condensate, elicit the full repertoire of cellular processing steps. In particular, the enabling of highly efficient escape from endosomes provides intracellular access to nanostructure-embedded biomolecular networks.

Cellular Defenses

We show how cellular defenses include nanoscale molecular interaction gating mechanisms that grant access on the formation of prescribed molecular assemblies that act as ‘access key codes’. The assembled molecular interactions at these gates may be captured and analyzed using time-resolved spatially localized chemical reactions within the cell, and the enabling assemblies analyzed in molecular detail.

Re-engineering Cell-Derived Condensates

The cell-derived condensate portion of the hybrid particles may be re-engineered to incorporate foreign proteins and RNAs while retaining overall function. The new biomolecules can then be delivered to intracellular locations with their function intact.

Understanding Nanostructure Architecture

These advances make it possible to understand the connection between nanostructure architecture and function, thereby opening the pathway to recapitulate the functional nanostructures using purely preparative methods.

Application of Functional Nanostructures

To apply these systems, we first propose to use functional nanostructures to deliver specifically optimized mRNA for the Covid-19 spike protein into the cell, optimizing mRNA metabolism to benefit from endogenous intracellular access.

Future Prospects

We then propose to engineer and deliver cooperative networks of multiple mRNA, with the prospect of being able to develop functional nanoscale therapies that can counter more extended dysfunctional networks such as those found in the tumor microenvironment.