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Revision as of 14:19, 13 July 2017
shRNA-induced Oncogene Silencing as a Therapeutic Avenue for Cancer
Columbia iGEM
The Advantages to a Synthetic Biology Approach
A cornerstone in synthetic biology is the connection of distinct biological functions to create useful system level behavior. We can take advantage of how bacteria naturally localizes in tumors while failing to survive in healthy tissue in the body to use bacteria as a cancer-specific delivery mechanism. Also, bacteria can mass produce products, invade cells, and release the products directly into the cells. This allows easily-degraded compounds to be effective delivered into cancer cells. It also prevents these compounds from affecting healthy cells. The combination of these mechanisms creates a powerful, cancer-specific circuit for gene therapy.
Expanding the Possibilities of Gene Therapy
Anticipating the applications of synthetic biology to healthcare, Columbia iGEM 2017 is devising a therapeutic approach to modulate mammalian gene expression at the post-transcriptional level. Recombinant E. coli with the capacity to invade mammalian cells will deliver an shRNA payload against an aberrantly expressed gene, for example an oncogene in cancer or proinflammatory cytokine in inflammation, to the host cytoplasm. This shRNA payload will then inhibit protein function, which can combat mutations that confer resistance to traditional therapies, as with the tyrosine kinase inhibitors gefitinib and imatinib.
The Future Outlook
Our mechanism to modulate mammalian gene expression can have a variety of applications, extending throughout as well as well beyond healthcare. The engineered bacteria would have a significant application to human health particularly in conditions characterized by aberrant gene expression, such as with oncogenes in cancer, cytokines in inflammation, and many others. For cancer applications, the engineered bacteria can be taken as an oral probiotic, which will then selectively localize in tumor cells to prove gene therapy.
