Speaker: Dr. Muthiah Manoharan | Moderation: Prof. Dr. Olivia Merkel (LMU)
Synthetic small interfering RNAs (siRNAs) are potent inhibitors of gene expression. These molecules are perfect examples of biomimetic chemistry as synthetic siRNAs act through the natural RNA interference (RNAi) pathway. To deliver therapeutic siRNAs into human liver, Manoharan and his team developed approaches that include chemical modification of the siRNAs and either lipid nanoparticle (LNP) formulation or multivalent N-acetylgalactosamine
(GalNAc) conjugation, making possible intravenous and subcutaneous administration, respectively. This presentation will cover the molecular basis of RNA therapeutics and their delivery including the chemical modifications and motifs used in each RNA strand to ensure uptake into cells of the targeted tissue, Ago2 recognition, silencing efficiency, metabolic stability, and safety.
- Muthiah Manoharan is Senior Vice President of Drug Discovery at Alnylam Pharmaceuticals, Cambridge (Massachusetts).