Intelligent Therapeutics and Metabolic Programming Through Tailormade, Ligand-Controlled RNA Switches; Final rept. 25 May 2005-24 Nov 2006

摘要

Cells employ sensor biomolecules to dynamically evaluate their environments and trigger appropriate metabolic responses. The ability to program cells with engineered molecules that sense structural and chemical events and translate these events to controlled cellular behavior is a critical technology for challenges present in medical research and biotechnology. Recent studies have demonstrated the prevalence and diversity of nucleic acids that function as sensors and regulators of gene expression. Recent efforts in nucleic acid engineering have succeeded in the generation of synthetic nucleic acid molecules that regulate gene expression through diverse mechanisms. The goal of this proposal is to develop a platform for the design of nucleic acid molecules that will program and control targeted cellular behavior Specific aims include to: (i) Design ligand-controlled RNA switches that regulate gene expression in mammalian systems; (ii) Construct engineered RNA switches that program cellular fates; (iii) Construct RNA switches that sense and respond to endogenous signals; (iv) Design RNA switches that detect viral infections in model systems; (v) Apply engineered RNA switches to the inhibition of expression of key viral and host proteins. The long-term objective is to develop enabling tools for programming cellular response for applications in intelligent therapeutics and metabolic reprogramming.