RNA drugs are an emerging class of therapeutics that address diseases at the genomic and/or transcriptomic level. Within this group, small interfering RNA (siRNA) and messenger RNA (mRNA) both enable regulation of intracellular protein concentrations. Following cytosolic delivery, siRNAs activate the RNA interference (RNAi) pathway leading to the sequence-specific silencing of genes at the post-transcriptional level, while mRNA can drive expression of therapeutic proteins. However, widespread clinical translation of RNA drugs is hampered by many extra- and intracellular barriers, including susceptibility to degradation and immune activation. Most importantly, RNAs are negatively charged macromolecules that cannot cross biological membranes, making cellular delivery challenging. As access to the cytosol of target cells is key to their therapeutic effect, efficient intracellular delivery of RNA drugs remains the most important barrier to overcome.
The research project of Bram consequently focuses on the development of a novel lipid nanoparticle platform for cellular delivery of RNA therapeutics, including siRNA and mRNA . More specifically, it merges the concept of drug repurposing, drug formulation into liposomal nanomedicines and their in vitro/in vivo application.