Gianneschi and coworkers have developed nanoparticles that serve to protect DNA from enzymatic degradation while facilitating cellular entry and are able to modulate mRNA levels in live human cells with no appreciable toxicity. This development represents a significant advancement towards non-toxic nucleic acid delivery systems that can be synthesized by simple protocols. However, as with many other biologically active nanomaterials, the mechanisms underlying, cellular uptake, endosome escape, mRNA regulation and nuclease resistance are not understood. Our goal is to develop a universally applicable method that will allow us and others to understand the mechanisms involved in nanomaterial uptake by cells. This will also enable us to identify potential bottlenecks that are associated with nanomaterial function and facilitate optimization of materials for downstream applications. Through a combination of advanced gene-editing tools and materials synthesis, we will discover new uptake pathways, optimize those pathways, and then utilize them to modulate gene expression allowing several routes towards treatment of disease including the sensitization of cells to therapies to which they are otherwise resistant. The proposed work is a fundamental biomaterials investigation of new structures, and new biological interfaces.
|Effective start/end date||7/1/17 → 5/31/20|
- National Science Foundation (DMR-1822422)