Research

Pioneering the next generation of diagnostic and therapeutic agents…

The Chaput lab at UCI specializes in the development of early stage drug discovery pipelines for future oligonucleotide therapeutics. We currently focus on two emerging modalities. The first is a category of molecules known as therapeutic aptamers, which are oligonucleotide sequences that mimic antibodies by folding into shapes that bind user-defined targets with high affinity. The second is a category of molecules known as DNA enzymes or DNAzymes, which are nucleic acid sequence capable of allele-specific gene silencing.

Members of the lab apply a team science approach to studying these molecules that involves bringing together individuals with a broad range of technical expertise that includes chemical synthesis, enzyme engineering, protein crystallography, and chemical biology. Through these activities, we aim to translate basic science discoveries into clinical applications.

Current research projects include:

improving the efficiency of XNA aptamer discovery and characterization
applying therapeutic aptamers to a broad range of biomedical problems
demonstrating robust & targeted knockdown of disease-associated proteins

Chemical Synthesis

Chemistry students in the lab are working to expand the repertoire of nucleic acid diversity through innovative solutions in nucleic acid chemistry. Specific examples, including changing the sugar moiety for improved biostability, and augmenting nucleobases with amino acid side chains for enhanced function.

Enzyme Engineering

The enzyme engineering team is applying a highly sophisticated microfluidics technique, known as droplet-based optical polymerase sorting (DrOPS) to re-engineer DNA polymerases for XNA synthesis activity. These enzymes are necessary for evolving artificial genetic polymers (XNAs) with desired functional properties that include ligand binding and catalysis.

Therapeutic & Diagnostic Agents

Molecular biology students in the lab are evolving functional XNAs with specific target binding affinity (aptamers) and catalytic activity (XNAzymes). Functional XNAs isolated from these selections are basis for diagnostic and therapeutic applications that can be applied to a broad range of biomedical targets.

Structure Determination

The structural biology team is working to solve X-ray crystal structures of engineered polymerases. Examining how these enzymes function at a molecular level is necessary for understanding their mechanism of action, which in turn will help guide the design of new XNA enzyme variants that function with enhanced activity.