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Overview: Research at the University of Washington Xenobiology Laboratory utilizes fundamental approaches in synthetic biology, chemical biology, biosynthesis, and biomolecular engineering for expanding the nucleic acid alphabet of life. We imagine a boundless future, not constrained by the 4-letter DNA alphabet (A, T, G, C) found in Nature. Instead, we work with a new lexicon, composed of natural (A, T, G, C) and synthetic letters (X, Y, W, Z). The overarching goal of our work is to radically transform how nucleic acids are used by humans in biotechnology and - by life itself.
What we do: Towards these goals, the Xenobiology research group develops XNA biotechnology for unnatural base pairing xenonucleic acids (ubp XNAs). Ubp XNAs are synthetic nucleic acids that basepair orthogonally to the canonical genetic code (i.e. ATGC+XYWZ) and can form the basis for an expanded genetic alphabet. The focus of our tool development is to bridge technological gaps in molecular biology that exist between standard DNA and expanded XNA. We then apply these tools to improve existing biotechnology, enhance biology, or explore emergent function created by large nucleic acid alphabets.
Future nucleic acid biotechnology - reimagined with XNA alphabets
Fundamental research areas
Sequencing - Developing next generation sequencing technology that is compatible with XNA alphabets.
Synthesis - Enzymatic synthesis of XNAs that can be used to rapidly, and cost effectively, access never-before-explored sequence space.
Synthetic biology - Genetic engineering bacteria that can replicate, transcribe, and translate XNAs for a 6-letter central dogma.
Biosynthesis and biocatalysis - Discovering enzymes that can be used to access XNA building blocks.
Active areas of application
Synthetic biology - XNA alphabets can be used to expand the genetic code of organisms for biomanufacturing.
Diagnostics and biosensing - XNA building blocks help us develop more sensitive and more specific nucleic acids for diagnostics and biosensing.
Digital information storage - XNA alphabets form the basis for high capacity (>3 bits/nt) digital information storage mediums.
Therapeutics - XNAs can endow nucleic acids novel function such as hyper stability (mxRNA vaccines), increased binding affinity (XNA aptamers), and improved reaction kinetics (XNAzymes).
Research fields: synthetic biology, biomolecular engineering, computer science, chemical biology, natural product discovery, biochemistry, chemical engineering, genetic engineering
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