Professor, Department of Pharmaceutical Sciences
School of Pharmacy & Pharmaceutical Sciences

Chemical Biology, Synthetic Biology, Polymerase Engineering, Oligonucleotide Therapeutics

Lab Website

Distinguished Mid-Career Faculty Award for Research (UCI Senate, 1 per year, 2022)
Selected speaker at the UCI Chief Executive Roundtable Meeting (2022)
Athalie R. Clarke Achievement Award (2021)
AAAS Fellow (2018)
Sigma Xi (2018)
W.M. Keck Foundation Awardee (2018)
ASU Faculty Award for Excellence in Defining Edge Research (2014)
Arizona Technology Enterprise Achievement Award (2013 – 2014)
National Institutes of Health EUREKA Award (2008-2012)
Howard Hughes Medical Institute Postdoctoral Fellowship (2001 – 2004)
University of California, Riverside, Graduate Fellowship (1994 – 2000)
National Collegiate Science Award (1994)

HHMI Postdoctoral Fellow, Harvard Medical School (2000-2004) with Jack Szostak

We are interested in developing the next generation of oligonucleotide therapeutics based on artificial genetic polymers commonly known as XNA's. Our approach is straightforward and involves engineering polymerases to synthesize diverse classes of XNA molecules with high activity and fidelity, and then using these enzymes as tools to discover XNA molecules with favorable drug-like properties for preclinical studies. We follow a team-science approach that incorporates diverse skill sets across a range of disciplines including organic chemistry, microfluidics, protein crystallography, and molecular biology.

Some of the questions we wish to answer include:
1. What is the impact of long-range interactions on polymerase engineering?
2. Can therapeutic aptamers achieve the same level of efficacy as therapeutic antibodies?
3. Can we identify more efficient paths for discovering functional XNAs?

Yu H, Zhang S, and Chaput JC* 2012. Darwinian evolution of an alternative genetic system provides support for TNA as an RNA progenitor. Nat. Chem. 4, 183-187.

Pinheiro VB, Taylor AI, Cozens C, Abramov M, Renders M, Zhang S, Chaput JC, Wengel J, Peak-Chew SY, McLaughlin SH, Herdewijn P, and Holliger P* 2012. Synthetic genetic polymers capable of heredity and evolution. Science 336, 341-344.

Larsen AC, Dunn MR, Hatch A, Sau SP, Youngbull C, and Chaput JC* 2016. A general strategy for expanding polymerase function by droplet microfluidics. Nat. Commun. 7, 11235.

Chim N, Shi C, Sau SP, Nikoomanzar A, and Chaput JC* 2017. Structural basis for TNA synthesis by an engineered TNA polymerase. Nat. Commun. 8, 1810.

Wang Y, Ngor AK, Nikoomanzar A, and Chaput JC* 2018. Evolution of a general RNA-cleaving FANA enzyme. Nat. Commun. 9, 5067.

Wang Y, Nguyen K, Spitale RC, and Chaput JC* 2021. A biologically stable DNAzyme that efficiently silences gene expression in cells. Nat. Chem. 13, 319-326.

Chim N, Meza RA, Trinh AM, Yang K, and Chaput JC* 2021. Following replicative DNA synthesis by time-resolved X-ray crystallography. Nat. Commun. 12: 2641.

Maola VA, Yik EJ, Hajjar M, Lee JJ, Holguin MJ, Quijano RN, Nguyen KK, Ho KL, Medina JV, Chim N, and Chaput JC* 2024. Directed evolution of a highly efficient TNA polymerase achieved by homologous recombination. Nature Catalysis. 7, 1173-1185.

Nguyen K, Malik TN, and Chaput, JC* 2023. Chemical evolution of an autonomous DNAzyme with allele-specific gene silencing activity. Nature Commun. 14, 2413.

American Chemical Society (ACS)

American Association for the Advancement of Science (AAAS)

Professor
Arizona State University 2014—2015

Associate Professor
Arizona State University 2011—2014

Assistant Professor
Arizona State University 2005—2011

Cellular and Molecular Biosciences

Chemical Biology

Chemistry

Pharmacological Sciences

Link to this profile
https://faculty.uci.edu/profile/?facultyId=6145

Last updated
02/26/2025