Design and Development of Novel Molecular Beacons for High-Precision T-Cell-Targeted mRNA and saRNA Delivery

Lipid nanoparticles (LNPs) are delivery vehicles approved for nucleic acid delivery, notably mRNA, as used in COVID vaccines. Although mRNA is a potent therapeutic, LNPs accumulate in the liver, limiting mRNA from broader clinical applications. To direct LNPs to other areas in the body, cell-specific antibodies (proteins created by our immune systems) may be attached to the LNP surface in a process called active targeting. However, the chemistry and fabrication process used for active targeting is inconsistent and difficult to manufacture, resulting in variable treatment efficacy.
To improve the consistency of active targeting LNPs, we propose a solution that leverages “click” chemistry, a process where two complementary components selectively bind to each other. First, a cell-specific antibody is administered to bind to the diseased cell to act as a beacon, followed by LNPs that click to the beacon. This process will ensure consistent antibody function, improving its targeting efficiency for more reliable LNPs. This work will broaden our understanding of how antibodies and LNPs interact with cells, allowing us to broaden the clinical applications of mRNA to fight cancers, autoimmune diseases, and other hard-to-treat conditions.