(270h) Encapsulation and Delivery of Biomolecular Therapeutics Using the Bacteriophage MS2 Viral Capsid

Glasgow, J., University of California, Berkeley
Tullman-Ercek, D., University of California, Berkeley
Francis, M., University of California Berkeley

The high specificity and vast diversity of proteins make them potential therapeutics for a wide variety of diseases. Unfortunately rapid clearance, immunogenicity, poor targeting, and endolysosomal degradation have rendered most proteins ineffective as drugs. Our labs have developed methods to encapsulate a wide variety of molecules inside the bacteriophage MS2 viral capsid. By disassembling the capsid into its constituent dimers and reassembling around negatively charged molecules, we have demonstrated the encapsulation of proteins, nanoparticles, polymers, and nucleic acids in a highly versatile, well-defined 27 nm protein shell. We are now applying this technique to the delivery of therapeutics to the cytoplasm of cancer cells using MS2 as a vehicle. The capsid has previously been shown to be an effective platform for targeted delivery of imaging agents, drugs, photodynamic therapy agents, and has even been shown to deliver biomolecules in cell culture. We are developing this system into a versatile device for delivery of any cargo molecule into the cytoplasm of cells via endocytosis and subsequent escape from the endosome. We are exploring this technique for use in triggering apoptosis in cancer cells by activating specific intracellular processes.