OligoNova Bridge - Uptake and Distribution of Oligonucleotide Constructs

Purpose and goal: To harness the potential that Oligonucleotide (ON) therapeutics brings

in delivering new treatments to patients where other pharmaceutical modalities have failed the network will start addressing two core challenges still in need of innovative solutions: cellular delivery (in particular endosomal escape) and distribution of ONs to different tissues/cell types for more exact delivery to the site of desired action.

Expected results and effects:

We aim to obtain data from the comparison of different conjugates with respect to their ability to escape endosomes and if this is cell type and sequence dependent. In addition, we expect to obtain data on tissue distribution of different lipid conjugates. The goal is that these results will feed into further developments of ON therapeutics.

Approach and implementation:

In this short project the focus is to compare a few selected approaches to ON delivery to achieve endosomal escape and tissue distribution. R&D will involve both RNA and DNA-targeting ONs. A number of group collborate to combine generation of oligonucleotide conjugates with

studies in different cell types and mice. This will generate an understanding on their applicability and pave the way for addressing other major challenges on therapeutic ONs in more long-term network collaborative projects.