Engineering M13 bacteriophage platforms for cancer therapy applications

Abstract

Two novel schemes for engineering M13 bacteriophage for application in the diagnosis, imaging and treatment of human tumors are proposed. Firstly, by exploiting the uniquely malleable biology of the M13 filamentous phage, we have engineered filamentous phages of shorter lengths by constructing our own set of small viral ssDNA that are packaged by M13 capsid proteins. These 'inho' phages can be sized to ~50nm and above in length. The small phage retains the M13 major and minor coat proteins which have previously been manipulated to serve as tethers to carry various therapy and imaging agents and target specific cancer sites. Now with the ability to control the aspect ratio of these rigid, rod-like phages we can further improve on M13 based cancer detection by optimizing for phage blood circulation and tumor extravasation. Secondly, we have added to our cancer targeting M13 platform collection by cloning for chlorotoxin display on the tail p3 capsid protein of M13. Chlorotoxin can induce passage across blood-brain barrier, targets for cancer cells, and specifically internalizes to glioma cells. Expression of chlorotoxin on M13 will allow us to capitalize on its strong affinity for tumors of neuroectodermal origin and expand the M13 therapy and imaging platform to tumor masses in the brain.