Novel DNA/RNA-regulated hammerhead ribozymes for biosensor applications

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This research aims to discover and protect (via patent) a novel method for RNA-based translational regulation, one that could provide an alternative to an existing popular method (toehold switching), which is patented. This, in turn, can be used for the development of cell-free, bio-sensors of pathogenic RNAs. The invention of a new method for translational regulation would present a non-trivial technical discovery. It opens the door to applications such as the monitoring and regulation of gene expression in vivo, in addition to the development by the partner company of kits/tools for pathogenic RNA (e.g., HIV and Hepatitis-C) detection, in human-sourced samples. The proposed method utilizes computationally designed trans-acting hammerhead ribozymes (taHHRzs), which would cleave a reporter gene transcript, unless special 'anti-cleaver' RNAs bind to a designated part of the taHHRz. This renders the taHHRz inactive, protecting the reporter gene transcript from cleavage, and allowing it to be translated to a visually detectable protein (or one that results in a detectable colored residue). In sum, the project's goals (both applied and academic) are well-defined; they require the development and optimization of a new method of translational regulation (outlined in the proposal); a fairly detailed plan of action and budget are presented; and the real-world implications of a satisfactory solution are clear and significant.