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A model of the chemical structure of a nucleic acid

PI: Thomas Brown

Department: Chemistry

Short strands of nucleic acids (oligonucleotides) perform a number of functions within the natural world, from encoding genetic information to templating the synthesis of key proteins. Researchers have sought to recreate such systems in the laboratory, whilst also finding new uses for oligonucleotides, such as in therapeutics, gene therapy, gene synthesis/editing (e.g. CRISPR) and molecular probes.

Existing methods for synthesising oligonucleotides on a laboratory and industrial scale rely on the use of complex biological systems. Adapting these methods to produce nucleic acid structures with non-natural motifs and functionality is often impossible, as the biological systems employed are inflexible and not tolerant to changes in environment or chemical functionality.

One of the most effective solutions to these issues has been developed by Prof Tom Brown at the University of Oxford and involves the use of chemical reactions, as opposed to biological systems, to generate bespoke sequences of nucleosides. This approach not only allows for greater customization, potentially allowing inclusion of non-standard nucleosides/bases, but the resulting oligonucleotides are more stable and have improved binding to interesting biological targets (mRNA, DNA etc.).

The underlying chemistry has been extensively investigated by the group and is protected by a portfolio of patent applications.

The IAA award will enable the gathering of data necessary to engage industrial partners and promote the scale up of the methodology.

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