UC Irvine

A major goal of synthetic biology is to recapitulate emergent properties of life. Despite a significant body of work, a longstanding question that remains to be answered is how such a complex system arose? In this dissertation, synthetic nucleic acid molecules with alternative sugar-phosphate backbones were investigated as potential ancestors of DNA and RNA. Threose nucleic acid (TNA) is capable of forming stable duplex structure with complementary strands of itself and RNA. This provides a plausible mechanism for genetic information transfer between TNA and RNA. Therefore TNA has been proposed as a potential RNA progenitor. Using molecular evolution, functional sequences were isolated from a pool of random TNA molecules. This implicates a possible chemical framework capable of crosstalk between TNA and RNA. Further, this shows that heredity and evolution are not limited to the natural genetic system based on ribofuranosyl nucleic acids. Structurally different from DNA and RNA, TNA was further explored as a source of nuclease resistant affinity reagents in therapeutic application. Since TNA molecules are naturally unavailable, synthetic approach has been developed previously for initial research explorations. A detailed synthetic optimization have been investigated in this dissertation to provide quantitative amount of TNA substrates for the downstream research applications in Synthetic biology.