Olivia Merkel, PhD - "Designing RNA Nanocarriers and Formulations by Machine Learning" - (Please note the unusual day)

Olivia Merkel, PhD
Professor of Drug Delivery
Vice-Director of the Department of Pharmacy
Ludwig-Maximilians-Universität München, Germany

Short CV

Abstract
Polymeric nanocarriers hold great promise for delivery of therapeutic RNA, yet the rational design of safe and efficient systems remains a major challenge due to the vast and complex polymer chemical space. This presentation will highlight recent advances in the development of biodegradable poly(β-amino ester) (PBAE)-based nanocarriers for RNA delivery. First, machine learning approaches trained on literature-derived datasets enabled the identification of novel amphiphilic polymers with high pulmonary gene silencing activity, significantly accelerating carrier discovery while reducing experimental screening efforts. Second, the integration of molecular dynamics simulations with machine learning in the “Bits2Bonds” platform established a virtual high-throughput screening framework for the de novo design and optimization of RNA nanocarriers and understanding endosomal escape. Finally, the translation of these systems toward inhalation therapy will be demonstrated using nebulizable micelle-embedded polyplexes for the treatment of idiopathic pulmonary fibrosis, including successful ex vivo gene silencing in human precision-cut lung slices. Together, these studies illustrate how artificial intelligence, computational modeling, and advanced formulation strategies can converge to accelerate the development of next-generation pulmonary RNA therapeutics.