Model-guided design of ligand-regulated RNAi for programmable control of gene expression.

ABSTRACT: Progress in constructing biological networks will rely on the development of more advanced components that can be predictably modified to yield optimal system performance. We have engineered an RNA-based platform, which we call an shRNA switch, that provides for integrated ligand control of RNA interference (RNAi) by modular coupling of an aptamer, competing strand, and small hairpin (sh)RNA stem into a single component that links ligand concentration and target gene expression levels. A combined experimental and mathematical modelling approach identified multiple tuning strategies and moves towards a predictable framework for the forward design of shRNA switches. The utility of our platform is highlighted by the demonstration of fine-tuning, multi-input control, and model-guided design of

SUBMITTER: Beisel CL 

PROVIDER: S-EPMC2583087 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature