Oligonucleotides such as messenger RNAs hold great promise as therapeutics in a vast number of diseases, ranging from genetic defects to cancer and infectious diseases. However, efficient oligonucleotide delivery is one of the most burning problems in biomedicine. At present we lack understanding of the structure of oligonucleotide delivery vectors, their interactions with cells and intracellular trafficking, and of their behavior in complex tissue environments.
The aim of this project is to develop super-resolution microscopy and correlative imaging workflows that will enable to paint the complete dynamic and ultrastructural picture of oligonucleotide delivery in cells and tissues. These workflows will provide a seamless integration of super-resolution microscopy (SMLM, STED), and electron microscopy (FIB/SEM and cryo-TEM) and will be used to relate ultrastructural information to the chemistry of delivery complexes, how it evolves during uptake and how this correlates with activity.
This four-year project is a collaborative effort between the Nanoscopy for Nanomedicine group led by Lorenzo Albertazzi
https://www.tue.nl/en/research/research-groups/nanoscopy-for-nanomedicine/ and the department of Medical BioSciences (Prof. Dr. Roland Brock/Prof. Dr. Nico Sommerdijk) at Radboud University. The project is funded through the 'Open Technology Program' of the Dutch Science Organization NWO and is supported by four companies in the area of microscopy and messenger RNA formulation and clinical application.