Aptamers—short DNA or RNA strands that grab specific targets—are being stitched directly into plastic-like polymers to create hybrid materials that combine the best of both worlds: the precision of biology with the durability of synthetic chemistry. This matters because current molecular recognition tools have frustrating trade-offs. Antibodies and enzymes are exquisitely specific but fragile, degrading in heat or harsh chemicals. Molecularly imprinted polymers are tough but often lack the pinpoint accuracy needed for reliable sensing or therapy. The Turner Group’s aptaMIPs have shown promise, but nobody understands exactly how the polymerisation process alters the aptamer’s structure and stability—a gap that limits commercial and clinical uptake. If this project succeeds, it will turn a promising prototype into a predictable, designable material. That could mean cheap, shelf-stable diagnostic sensors that work in remote clinics, or therapeutic agents that resist degradation in the body. The researchers are testing their approach on two concrete cases: aptamers for prion proteins and for an existing macular degeneration drug. This is fundamentally a fundamental science project—it aims to understand the physicochemical rules governing these hybrids—but that understanding is the prerequisite for turning clever chemistry into reliable technology.
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Molecular recognition - the interaction between two entities at the molecular scale - is vital to nearly all biological processes and scientists have harnessed this for numerous applications. In many cases antibodies and enzymes are used to great effect but these biological based materials have inherent issues including immunogenicity and environmental stability, limiting wider functionality. Molecular imprinting involves making a binding pocket inside a polymer which is chemically and shape specific for the target compound. These "smart plastics" offer robustness compared to biological molecular recognition elements such as antibodies and enzymes. They also can work in extreme environmental conditions. However, they sometimes lack the necessary specificity/affinity. Aptamers are small pieces of DNA/RNA that can selectively target proteins and/or small molecules and bind to them with high specificity and affinity. They are not toxic and are attractive alternatives to antibodies. They have been used primarily in research due to their susceptibility to enzymatic and chemical degradation, though this is slowly changing, and they are becoming commercially relevant. The Turner Group has recently developed hybrid materials that create a "best-of-both-worlds" approach incorporating aptamers into molecularly imprinted polymers (MIPs) making aptaMIPs. In simple terms, the aptamer structure is modified to allow it to be directly incorporated into a polymer, so it will hold its shape while being protected from environmental conditions. Novel, high affinity and stable materials were created, with the capability to match biological materials in terms of affinity and selectivity. https://doi.org/10.1039/D1PY00607J & https://doi.org/10.1002/gch2.202200215 While the principle of these hybrids has been demonstrated, our understanding of how the process affects the structure and stability of both components (nucleic acid sequence and polymer) is not understood. This project will explore the fundamental physicochemical properties of these with the key aim of improving the capabilities of this class of synthetic molecular recognition material making them more attractive for commercial and clinical use. Working alongside the Craggs group - specialists in the development and application of single- molecule fluorescence techniques and their use looking at molecular structure and dynamics (https://doi.org/10.1038/s41592-023-01807-0 & https://doi.org/10.1016/j.bpr.2021.100013)- we will look at how the nucleic acid sequences respond to the polymerisation process, with a particular focus of stability and structural changes. This project will use a wide range of analytical techniques including, but not limited to, Differential Scanning Calorimetry, Isothermal Calorimetry, Circular Dichroism, single-molecule Forster Resonance Energy Transfer, Nuclear Magnetic Resonance, Surface Plasmon Resonance and Thermal Gravimetry; alongside synthetic techniques (polymer and nucleic acid) to explore these materials. We will focus our efforts on producing aptaMIPs for clinically relevant systems: firstly, on aptamers that recognise prion proteins; and secondly on an existing known therapeutic aptamer for macular degeneration. These will offer impact for this fundamental study.
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