Developing Artificial Genetic Polymers for Synthetic Biology and Molecular Medicine
- John C. Chaput (Arizona State University)
Abstract
Synthetic biology holds great promise as a scientific discipline with practical applications in material science, human health, and the environment. However, the potential for dualuse applications has raised new concerns about the safety of using DNA as an engineering tool for synthetic biology. One possible solution to this problem is to develop a firewall that impedes the exchange of genetic information between synthetic biology and natural biology. This could be done, for example, by creating orthogonal life forms that carry genetic information in the form of synthetic genetic polymers (termed ‘xeno nucleic acids’ or XNA) that store genetic information in the canonical bases of adenine (A), thymine (T), cytosine (C), and guanine (G), but use a backbone structure that contains a sugar other than ribose or deoxyribose. Such systems would render genetic messages invisible to nature, because the enzymes that make and degrade DNA do not recognize XNA. While the appearance of orthogonal life forms may be years away, progress towards this long-term goal has given rise to engineered polymerases that can copy genetic information back and forth between DNA and certain XNA polymers. These systems have immediate practical applications in molecular medicine where a critical need exists for nuclease resistant affinity reagents (aptamers) and catalysts that can function in complex biological environments. In this talk, I will provide a model for how orthogonal life forms could be developed, and describe recent advances in the replication of XNA polymers.
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