The Chaput laboratory 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.