Ming Zhao

My lab’s mission is to advance cutting-edge technologies at the interfaces of functional materials and biology to address grand challenges in human health. A major research goal is to design and develop advanced systems and materials that enhance protein delivery to a range of anatomic sites for gene therapy, metabolic disease and cancer treatment, and biosensing applications. The following topics are most representative of our current research interests in this space.

1. Non-viral delivery of CRISPR system components for precision genome surgery.

The advent of gene-editing technology has transformed unprecedentedly many aspects of disease diagnosis and treatment, as well as drug discovery. Successful therapeutic genome editing requires the ability to efficiently and safely deliver gene-editing components into desired cells. Unlike viral vectors, which are associated with the risk of insertional mutagenesis and immunogenicity, non-viral delivery of gene-editing agents in protein formats minimizes genome exposure to these agents, thereby significantly reducing the potential for off-target editing. We seek to leverage cutting-edge nanotechnologies to advance the development of next-generation nanovehicles for the CRISPR ribonucleoprotein (RNP) delivery, enabling precise repairs of genetic disorders.  

2. Oral protein delivery using gastrointestinal (GI)-resident dosage forms

Proteins orchestrate a diverse array of critical biological processes. Imbalances in protein activity and concentration within the GI tract form the basis of various digestive and absorption disorders, potentially leading to the buildup of deleterious metabolites in the intestine or bloodstream. Oral protein replacement therapy has the advantages of noninvasiveness and avoidance of immune reactions frequently associated with systemic injections. However, traditional oral formulations have limitations in targeting ability, short retention time and poor bioavailability. To overcome these barriers, we aim to design and develop GI-resident microdevices for protein delivery, achieving precise regional targeting, prolonged retention time, and sustained drug release. We anticipate these innovations will significantly enhance the diagnosis and treatment of metabolic disorders and cancers in the GI tract.

3. Engineering bio-electrochemical interface toward real-time and continuous monitoring of multianalytes in vivo.

The capability to simultaneously monitor multiple biochemicals in vivo in near-real-time, with high selectivity and spatial resolution, has triggered significant research interest. Simultaneous multianalytes detection requires selective deposition of various biological receptors (such as proteins, cells, or DNA) onto specific sites of a microelectrode array (MEA) microprobe, typically achieved through manual loading. However, the manual approach can be problematic when the MEA feature size is in the micrometer range. Our focus will be on innovating biomolecule patterning and immobilization techniques to create MEA microprobes with high spatial resolution and sensitivity.