Protein Delivery

Bioreversible Esterification for the Intracellular Delivery of Proteins via Lipid Nanoparticles

 

Protein delivery, compared to nucleic acid delivery, offers immediate therapeutic effects, controlled dosing, lower risk of genome integration, and smaller-sized cargo (e.g., the molecular weight of myoglobin protein is ~17KDa, while that of mRNA is ~370 KDa). This underscores the pressing need for an innovative therapeutic platform tailored for intracellular protein delivery in vivo. Many approaches exist to facilitate protein delivery into cells, but most strategies are incompatible with in vivo settings. We are interested in utilizing in vivo compatible drug carrier such as LNPs and liposomes that have revolutionized nucleic acid-based drug delivery in vivo and in the clinic, for protein delivery. To date, protein-based drugs have not been suitable for LNP technology because of their diverse size, shape, and charge. We are interested in developing highly modular and general bioconjugation chemistry­–bioreversible protein esterification–to tailor protein surface properties without the need for genetic engineering.