John Charles Chaput

Picture of John Charles Chaput
Professor, Department of Pharmaceutical Sciences
School of Pharmacy & Pharmaceutical Sciences
Ph.D., University of California, Riverside, 2000, Chemistry
M.S., University of California, Riverside, 1995, Chemistry
B.S., Creighton University, 1994, Chemistry
University of California, Irvine
Irvine, CA 92697
Research Interests
Chemical Biology, Synthetic Biology, Polymerase Engineering, Artificial Genetic Polymers
Academic Distinctions
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
Research Abstract
We are interested in evolving enzymes (polymerases, ligases, kinases, and nucleases) that can synthesize and modify artificial genetic polymers (XNAs) in the same way that natural enzymes synthesize and process DNA and RNA. Our goal is to use these enzymes to study the synthetic biology of artificial genetic polymers so that we can: 1) improve our understanding of how enzymes work, 2) investigate fundamental questions about life's genetic system, and 3) establish new diagnostic and therapeutic agents that improve human health and disease detection. This is a highly interdisciplinary environment where students learn state-of-the-art techniques in synthetic organic chemistry, microfluidics, X-ray crystallography, and directed evolution, and apply this knowledge to innovative projects that advance the emerging field of synthetic genetics.

Some of the questions we wish to answer include:
1. Why did nature choose DNA (and RNA) as the molecular basis of life's genetic system?
2. What are the determinants of polymerase specificity and how can this information be used to generate engineered polymerases that are highly efficient and specific for XNA substrates?
3. Can we engineer XNA polymerases that amplify XNA using the polymerase chain reaction?
4. Can we close the gap between antibodies and aptamers as therapeutic agents?
5. Can we use XNA enzymes as allele-specific gene silencing agents or as reagents for disease diagnosis?
Available Technologies
Selected Publications:
1. Wang, Y., Ngor, A., Nikoomanzar, A., and Chaput, J.C.* 2018. Evolution of a general RNA-cleaving FANA Enzyme. Nature Communications 9, 5067.

2. Pinheiro, V.B., Taylor, A.I., Cozens, C., Abramov, M., Renders, M., Zhang. S., Chaput, J.C., Wengel, J., Peak-Chew, S-Y., McLaughlin, S.H., Herdewijn, P., and Holliger, P.* 2012. Synthetic genetic polymers capable of heredity and evolution. Science 336, 341-344.

3. Yu, H., Zhang, S., and Chaput, J.C.* 2012. Darwinian evolution of an alternative genetic system provides support for TNA as an RNA progenitor. Nature Chemistry 4, 183-187.

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

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

6. Wang Y, Nguyen K, Spitale RC, and Chaput JC. A biologically stable DNAzyme that efficiently silences gene expression in cells. Nature Chemistry 2021, 13, 319-326.
Professional Societies
American Chemical Society (ACS)
American Association for the Advancement of Science (AAAS)
Other Experience
Arizona State University 2014—2015
Associate Professor
Arizona State University 2011—2014
Assistant Professor
Arizona State University 2005—2011
Graduate Programs
Cellular and Molecular Biosciences
Chemical Biology
Pharmacological Sciences
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