A central challenge in nucleic acid therapeutics is how to deliver genetic cargo efficiently while avoiding immunotoxicity which limits clinical translation. Lipid nanoparticles (LNPs) are effective delivery systems for mRNA and DNA. However, the positive charges of their ionizable lipids stimulate several immune pathways while also being crucial for endosomal escape. To mitigate this, new chemical space must be explored. Our lab develops next-generation lipid nanoparticle systems that do not stimulate the immune response. These novel lipids are able to efficiently encapsulate nucleic acids and escape endosomes while not stimulating immune pathways like traditional ionizable lipids do.
