An RNAi-Enhanced Logic Circuit for Cancer-Specific Detection and Destruction
Abstract
We seek to design and implement a genetic circuit that based on multiple genetic markers is able to selectively recognize and destroy cancer cells, leaving healthy cells unaffected. In this project we focus on the MCF-7 breast adenocarcinoma cell line, a well-characterized cell line derived from a common form of breast cancer. MCF-7 cells overexpress Gata3, NPY1R and TFF1 mRNA relative to healthy cells. Based on our bioinformatics analysis, taking into account the three biomarkers allows for dramatically improved specificity in comparison to targeting single genes. We therefore design our circuit so that it only targets for destruction cells with high levels of mRNA of all three biomarkers (an AND gate). We have tested and successfully implemented each of the necessary circuit components: very efficient siRNA and microRNA gene knockdown, hBax dependent apoptosis, expression of mStaple (a short regulatory mRNA), and non-integrating lentivirus. Our current efforts are focused on careful characterization of the modules as a preliminary step for final implementation and fine-tuning of the full circuit. In the next step we will introduce all of the circuit components into HEK 293 and MCF-7 cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2011
- Accession Number
- ADA553119
Entities
People
- Ron Weiss
Organizations
- Massachusetts Institute of Technology