UCLA researchers in the departments of Medicine, Microbiology, Immunology & Molecular Genetics, and Bioengineering have developed a novel method for loading protein payloads into vault nanoparticle carriers.
Vaults are naturally occurring nanoparticles that are widely present in eukaryotes. There is significant interest in developing these materials as delivery vehicles for small molecules, proteins, or antigens as vaccine vectors. Methods currently in use for loading biomolecules include modification of the protein of interest with a vault-binding domain, or direct genetic fusion to the major vault protein itself. However, these methods are inconsistent, require lengthy optimization processes, or interfere with vault assembly. Developing methodology to load protein payloads into vaults will therefore be critically important to their use as protein delivery vehicles.
Prof. Yang and coworkers have developed a novel method for loading protein payloads into vault nanoparticle carriers. A specific region in the vault structure has been identified where the amino acids are disordered. Because this region is flexible, the area can be tolerant of protein insertions. Proof of concept has been demonstrated by genetic insertion of proteins into the disordered loop with subsequent incorporation of desired sequences. No disruption of normal vault morphology was observed.
Proof of concept has been demonstrated by inserting a restriction enzyme site into the disordered loop.
Vaults, protein delivery, protein engineering, fusion protein, vaccine, antigen delivery