STRUCTURAL DESIGN OF THERAPEUTIC NANOPARTICLES

Non-viral delivery of therapeutic nucleic acids is a critical challenge for nanomedicine, one that has a heightened spotlight with the recent development of RNA COVID-19 vaccines and primed to conquer more devastating diseases. Therapeutic nucleic acids including plasmid DNA, microRNA, messenger RNA, and CRISPR-Cas9 offer the immense potential of altering gene expression to cure disease, but the major hurdle of delivery stands in the way. Designing nanoparticles for delivery is crucial, as the size and chemical composition of DNA and RNA limit transfection and are susceptible to enzymatic degradation. 

We have developed precise size scaling laws and exposed stability dependencies on molecular structure, showing that polymer and nucleic acid design control nanoparticle morphology, size, and stability; all crucial design parameters that affect stealth, biodistribution, and cell uptake. However, the current state of structure-property relationships for nucleic acid nanoparticles is still limited and falls short of predicting nanoparticle function in complex biological environments.

Translating structure-property relationships to clinical conditions is an unmet need. Designing for encapsulation, transport, targeting, and release requires extensive material characterization and a thorough understanding of the molecular nuances of polymer interactions. We build nucleic acid delivery systems with programmable targeting and controlled release capabilities by translating rigorous physical characterization to clinical applications.