20.109(F09): Omar Abudayyeh and Pablo Crespo Research Proposal

= Engineering phages to target tumors = Omar Abudayyeh and Pablo Crespo

Project Overview
This project aims to engineer phages that are able to selectively target cancer cells in vitro and deliver cargo that can result in tumor death. Because phages have multiple types of proteins on their outer coat, the phages can be designed to bind to other substrates, such as drugs or gold, in addition to the tumor. This allows for targeted delivery of drugs or for photothermal cancer therapy through irradiation of the gold.

Research Problem and Goals
The goal of this project is to develop phages that can be used as constructs for delivering cargo to tumors in mice. As with gold nanoparticles, phages offer a construct for modifiable attachment of cargo, such as drugs or gold, for delivery to tumors. Phages can have benefits, however, such as longer circulation times due to their shape. Moreover, while nanoparticles require ligands that bind to known tumor-associated antigens, with phages we only need to screen a phage library to isolate phages that selectively bind to tumors. In addition to designing phages that can bind to both tumors and cargo, including drugs and gold, we will test their therapeutic effect in mice and attempt to increase phage circulation time using polyethylene glycol (PEG).