Computationally designed proteins for receptor targeting and delivery of macromolecules

Medical solutions that help protein therapeutics accumulate into cells and the brain are crucial for future development of biotherapeutic treatments.

Protein-based therapeutics have a tremendous potential to treat disorders that so far have only been the domain of small molecule drugs. However, their efficacy has been severely restricted.

To reach into cells and the brain, macromolecules have to traverse the cell membrane (CM) or get across the blood–brain barrier (BBB).

These are basically impenetrable for large molecules, which necessitates better delivery systems to enhance exposure of therapeutics across biological barriers. It would be advantageous to achieve it in a methodical way based on clear-cut principles guiding delivery.

We present an approach where we coat capsid nanoparticles to interact with membrane receptors, and where the lumen of the particles is preloaded with macromolecular biotherapeutics.

Upon interaction and subsequent internalization, the capsid dissociates apart to deliver the cargo inside biological compartments.

We apply our methodology to the membrane surface receptor used by transferrin, but the developed system can easily be modified for any receptor of interest.

Additionally, we investigate mechanistic pathways by carrying out single cell genomics experiments to devise more knowledge-based delivery systems. The inventiveness of our approach has the potential to transform the efficiency of protein drugs.