Imagine being able to diagnose and destroy diseased cells using RNA. This can be accomplished by using RNA strand displacement cascades that recognize certain mammalian cell-specific biomarkers, such as characteristic mRNA strands or metabolites, use these as abstract inputs to digital logic cates, and then yield a wide array of desired outputs. We propose a new method of implementing the paradigm
s of sensing, processing, and actuation inside mammalian cells by applying the mechanism of DNA strand displacement from the field of nucleic acid computation to RNA. Traditional synthetic biology approaches seem to have hit a barrier in terms of the number of regulatory components that can be used predictably and reliably, limiting the complexity of cellular circuits. On the other hand, the strand displacement method of molecular computing within mammalian cells is highly modular, scalable, and orthogonal. We have demonstrated that RNA can be used as a processing medium, and have proposed novel in vivo NOT gates, which along with AND and OR gates can directly be produced inside mammalian cells. Currently, we are developing modeling platforms to explore kinetics of strand displacement reactions in vivo, as well as designing actuation systems that allow the RNA logic to interface with a variety of protein outputs. Our integrated approach can fundamentally impact the fields of biological engineering, biomedical engineering, and medical diagnostics. Thank you to our sponsors: MIT EECS, MIT BE, iGEM, Alnylam Pharmaceuticals, Genious, Genewiz, New England Biolabs, Addgene, Genscript, MIT ChemE, Pfizer, EBICS, MIT EHS, Monsanto, Flagship Ventures, Third Rock Ventures and Integrated DNA Technologies.
