Optimizing mRNA Delivery with Targeted Elastin-Like Polypeptide-Based LENN Formulations
- LENN comprised of elastin-like polypeptide-epidermal growth factor fusion proteins (ELP-EGF) and cyclodextrin-peptide conjugates form stable mRNA complexes that efficiently deliver their cargo to the cytosol of EGFR+ bladder tumor cells in vitro and in vivo
- Multiple reaction monitoring HPLC-MS lipidomics analysis, pharmacologic inhibition, and EGF blockade experiments indicate that EGF-bearing mRNA LENN enter EGFR+ cells via clathrin-mediated endocytosis, with no significant changes to other lipid pathways that would indicate off-target effects or immune responses
- Addition of 10% glycerol and lyophilization enables the long-term storage of mRNA LENN complexes, with full retention of activity after rehydration