About John Chaput
John Chaput is Professor of Pharmaceutical Sciences, Chemistry, and Molecular Biology and Biochemistry at the University of California, Irvine (UCI). He graduated in 1994 from Creighton University with a bachelor’s degree in chemistry and earned his Ph.D. in 2000 from the University of California, Riverside. For his Ph.D. thesis, he studied the molecular recognition properties of unnatural nucleic acid polymers. Under the guidance of Chris Switzer, he designed, built, and characterized the first five-stranded DNA helix that self-assembles around a metal-nucleated iso-guanine motif. From 2000-2004, he was an HHMI Post-Doctoral Fellow in Prof. Jack Szostak’s laboratory at Harvard Medical School. While at Harvard, he studied the de novo evolution of functional proteins by mRNA display and developed early methods for synthesizing artificial genetic polymers using commercial polymerases. In 2004, he became Assistant Professor of Chemistry and Biochemistry at Arizona State University (ASU). He was promoted to Associate Professor in 2011 and Full Professor in 2014. From 2004 to 2015, he was a core faculty member of the Biodesign Institute at ASU, and from 2011-2014 served as Deputy Director of the Center for Evolutionary Medicine and Informatics (CEMI). In 2015, he moved his laboratory to UCI, where he develops enzymes that can manipulate artificial genetic polymers (commonly referred to as XNAs) in a manner analogous to the enzymes provided by nature. The overarching goal of his research is to develop the next generation of diagnostic and therapeutic agents using XNAs that are biologically stable and responsive to Darwinian evolution by in vitro selection.
The Chaput Lab studies fundamental and applied problems at the interface of chemical and synthetic biology.
Synthetic biology encompasses a wide range of molecular biology tools that enable researchers to precisely manipulate the DNA sequence within a gene, gene cluster, or genome. Recent developments, however, have made it increasingly possible to generate man-made enzymes that can perform similar functions on artificial genetic polymers that are distinct from those found in nature (DNA and RNA). Collectively referred to as xeno-nucleic acids, or XNAs, these genetic polymers have unique physicochemical properties that include resistance to nuclease digestion and expanded chemical functionality. We envision a future where many of the same synthetic biology tools available to manipulate DNA and RNA are available to manipulate XNA. Such efforts open the door to a vast new world of synthetic genetics, where artificial genetic polymers can be used to create new tools for biotechnology and medicine, and possibly even improve our understanding of the origin of life itself.
While the possibility of manipulating XNAs in a test tube has enormous potential for new applications in biotechnology and medicine, several challenges must be overcome before such achievements can be realized. The most significant challenges include:
- Establishing new chemical synthesis strategies that produce XNA monomers on the gram to multi-gram scale and expand the chemical functionality of XNA beyond the natural bases of adenine (A), cytosine (C), thymine (T), and guanine (G).
- Designing new molecular evolution approaches that facilitate the production of XNA enzymes that can recognize and modify XNA substrates with high catalytic efficiency.\
- Developing automated approaches that enable the rapid discovery of XNA aptamers and XNA catalysts to a broad range of biologically important targets.
- Elucidating the molecular structures of XNA enzymes and in vitro selected XNA aptamers and XNA catalysts to high resolution.
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