The Rouge Group’s research focuses on the improving the delivery of RNA and DNA into cells. Recently, the news has focused on the Moderna and Pfizer vaccines, which are designed to deliver mRNA into cells to encode the viral proteins that the immune system needs to recognize and fight off infections. In a similar fashion, the Rouge Group has been developing nanocarriers designed to maximize the delivery of short RNA and DNA molecules into cells that can silence genes involved in disease pathways. The greatest challenges surrounding the delivery of these molecules into cells is their chemical instability (i.e. RNA can only last a few minutes in cells and must be stored at ultra-cold temperatures prior to use) and our ability to get the RNA and DNA to the right cell types.

Recently, Dr. Jessica Rouge was awarded an R35: Maximizing Investigators’ Research Award (MIRA) for Early Stage Investigators grant from the NIH’s National Institute of General Medical Sciences (NIGMS). The award, titled “Achieving enhanced cytosolic delivery and greater efficacy of therapeutic nucleic acids using DNA-surfactant conjugates,” is for $2,000,300 over a 5-year period.

This grant focuses on addressing the critical need for improving the delivery of RNA and DNA molecules to the interior of cells, with a specific focus on nucleic acids that have the ability to treat diseases. These include molecules such as DNAzymes, siRNA and other antisense oligonucleotides that target the mRNA of cells for silencing genes involved in disease pathways. These mRNA are found in the cytosol, and a number of biological barriers need to be overcome to achieve efficient delivery.

The Rouge Lab has a multi-tiered set of chemical approaches to address these issues, ranging from synthesizing new DNA surfactant conjugates that aid in penetrating cell membranes, to the synthesis and use of hybrid nanomaterials for stabilizing oligonucleotides, to the application of enzymes for tailoring the assembly of these materials. The grant will also support the synthesis of new fluorophore-labeled surfactants for assaying the efficiency of nucleic acid delivery into cells and the rate of endosomal escape – two traditionally challenging areas to study due to the chemical instability of RNA and DNA in the cytoplasm of cells.

With the funding from the NIH, the Rouge Group seeks to develop an improved nucleic acid delivery platform that can lead to potentially more effective RNA and DNA treatments, in which less therapeutics can be utilized with a more effective outcome.