High-throughput in vivo screening of extra-hepatic lipid nanoparticles enabled by machine learning design of novel chemistry

ESGCT 2024 Poster – The promise of nucleic acid-based therapeutics is immense for treating a wide range of diseases.  The challenge lies in the ability to deliver these therapies to their intended sites in body, ideally specifically and efficiently. Lipid nanoparticles (LNPs) have emerged as a powerful tool for delivery due to their ability to encapsulate and protect nucleic acids and facilitate their entry into cells.  With the approval of ONPATTRO and COVID mRNA vaccines, most development is limited to liver indications and vaccines. Most LNPs accumulate in the liver when administered systemically with no or limited exposure in other tissues and organs. Liberate Bio is hoping to realize the full potential of nucleic acid medicines by building nanoparticle chemistries using novel cationic ionizable lipids to unlock delivery to extrahepatic tissues. We have developed a high-throughput pooled biodistribution assay focused on non-human primates enabling us to screen as many as 96 formulations simultaneously in a single dosing. This has enabled us to generate large amounts of high-quality data in a short timeframe to supply the curated data requirements for improved Machine Learning models.