Engineering M13 bacteriophage platforms for cancer therapy applications

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.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Mechanical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2015

Author dc:creator

• Tsedev, Uyanga

Advisor dc:contributor.advisor

• Angela M. Belcher and Alan J. Grodzinsky.

• Mechanical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/103838

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/103838