An RNAi-Enhanced Logic Circuit: Cancer-Specific Detection and Destruction

The Princeton University iGEM 2007 team, consisting of 10 undergraduate students, 2 high school students, and 8 instructors, envisions a paradigm shift in the way one can target cancer and destroy the resulting cancerous cells.

Using standard engineering practices, we have designed, and are in the process of implementing, a novel system that utilizes RNA interference (RNAi) to detect and destroy cancer cells in a tissue-specific manner. We are interfacing RNAi components together with promoter and repressor elements to form logic circuits, which allow the use of multiple criteria to target cancerous cells in a unique and highly specific manner. As a measure of safety, we utilize mutant lentiviral integrase to deliver our construct into the cell as a non-integrated plasmid, preventing any disruptive effects that could be attributed to pseudorandom integration by the lentivirus. This also ensures that the daughter cells will not inherit the cancer-detecting circuitry, thus preventing unintended proliferation of our construct and allow for more extensive and comprehensive cancer treatments.

We have constructed many components of our system and are in the process of testing our plasmids in a proof of concept manner. Where possible, we will revise and improve upon our components based on mathematical modeling and experimental results. Lab work, including experimentation, bioinformatics, and simulations, and literature have been used as feedback mechanisms to improve the implementation of the designed systems.

Please see the extended overview for more information.

Team members

• Anand Atreya
• Bashir Geer
• Caroline DeHart
• Justine Chiu
• John Mangual
• Robert Loughlin
• Oly Khowash
• Ritu Kamal
• Sanjiv Goli
• Safiyy Momen
• Stephen Riutta
• Ted Lee
• Wei Ho
• Andrew Sichel

• Ron Weiss [http://www.princeton.edu/~rweiss Website]
• Ihor Lemischka [http://www.molbio.princeton.edu/research_facultymember.php?id=25 Website]
• Cil Purnick Contact Cil
• Christoph Schaniel
• Sairam Subramanian
• Ernesto Andrianantoandro
• Steve Firsing
• Leor Weinberger

Overview

An RNAi-Enhanced Logic Circuit: Cancer-Specific Detection and Destruction

The Princeton University iGEM 2007 team, consisting of 10 undergraduate students, 2 high school students, and 8 instructors, envisions a paradigm shift in the way one can target cancer and destroy the resulting cancerous cells.

Using standard engineering practices, we have designed, and are in the process of implementing, a novel system that utilizes RNA interference (RNAi) to detect and destroy cancer cells in a tissue-specific manner. We are interfacing RNAi components together with promoter and repressor elements to form logic circuits, which allow the use of multiple criteria to target cancerous cells in a unique and highly specific manner. As a measure of safety, we utilize mutant lentiviral integrase to deliver our construct into the cell as a non-integrated plasmid, preventing any disruptive effects that could be attributed to pseudorandom integration by the lentivirus. This also ensures that the daughter cells will not inherit the cancer-detecting circuitry, thus preventing unintended proliferation of our construct and allow for more extensive and comprehensive cancer treatments.

We have constructed many components of our system and are in the process of testing our plasmids in a proof of concept manner. Where possible, we will revise and improve upon our components based on mathematical modeling and experimental results. Lab work, including experimentation, bioinformatics, and simulations, and literature have been used as feedback mechanisms to improve the implementation of the designed systems.

Please see the extended overview for more information.

Previous work