Enhancing the biocompatibility and potency of lipid nanoparticles (LNPs) by refining the structure of ionizable lipids through an iterative method. Problem: Ionizable lipids play a crucial role in determining the potency and biocompatibility of LNPs. Current approaches, medicinal chemistry, and combinatorial chemistry, each have limitations. Medicinal chemistry is laborious and low throughput, while combinatorial chemistry often fails to produce lipids that are both potent and biocompatible. Solution: The innovative approach combines the strengths of medicinal and combinatorial chemistry, resulting in a highly efficient method that generates potent and biocompatible lipids, termed "UPenn Lipids." Many of these lipids surpass the performance of currently approved ionizable lipids. Technology: Leveraging the benefits of both traditional approaches, the method utilizes an A3-coupling reaction to introduce significant diversity in lipid structures. This diverse pool undergoes screening for biocompatibility and potency, with the most favorable lipids selected. The process iterates, culminating in a technique known as directed chemical evolution. Advantages:
Stage of Development:
Successive stages in the iterative process of directed evolution, which can be reiterated continuously until lipids with desirable characteristics are achieved. Intellectual Property:
Desired Partnerships:
Docket: 24-10535