I-Corps: Identification of a stable hybrid carrier for large-scale expression of recombinant miRNAs and siRNAs in E. coli

University Of California-Davis, Davis CA

Investigators

Abstract

The broader impact/commercial potential of this I-Corps project focuses on the development of a high-yield, cost-effective production platform for natural RNA interference (RNAi) agents. This project addresses the increasing interest in developing natural RNA-based agents for therapeutics and translational research. Since RNA-based drugs have the capability to approach targets (such as small molecules and proteins) that are unavailable by other methods, this project will open new directions for treating incurable diseases with naturally produced drugs. With the use of fermentation technology, this research may result in the cost-effective production of natural RNA-based drugs for both academic research institutes and pharmaceutical companies. If successful, this project will establish a novel RNAi bioengineering platform. This I-Corps project is based on the identification of a stable, fully humanized hybrid carrier for large-scale expression of recombinant micro RNA (miRNA) and small interfering RNA (siRNA) in a common strain of E. coli. Current RNA interference (RNAi) research and development is often limited to the use of chemically-engineered or synthesized RNAi agents that require various and extensive artificial modifications for stability. These artificial modifications can provoke immunogenicity. The overall purpose of this project is the development of a unique platform for the economical and sustainable production of natural RNAi agents that are produced and folded in living cells. Early work has demonstrated that bioengineered miRNA/siRNA agents carry few natural post transcriptionally-modified nucleosides and exhibit favorable stability within human cells and mouse models. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.