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Genetically encodable materials for non-invasive biological imaging

Abstract

Many questions in basic biology and medicine require the ability to visualize the function of specific cells and molecules inside living organisms. In this context, technologies such as ultrasound, optoacoustics and magnetic resonance provide non-invasive imaging access to deep-tissue regions, as used in many laboratories and clinics to visualize anatomy and physiology. In addition, recent work has enabled these technologies to image the location and function of specific cells and molecules inside the body by coupling the physics of sound waves, nuclear spins and light absorption to unique protein-based materials. These materials, which include air-filled gas vesicles, capsid-like nanocompartments, pigment-producing enzymes and transmembrane transporters, enable new forms of biomolecular and cellular contrast. The ability of these protein-based contrast agents to be genetically encoded and produced by cells creates opportunities for unprecedented in vivo studies of cellular function, while their amenability to genetic engineering enables atomic-level design of their physical, chemical and biological properties.

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Fig. 1: Small proteins as genetically encoded contrast agents for non-invasive imaging.

panel e adapted with permission from ref. 22, Springer Nature Ltd.

Fig. 2: Proteinaceous nanocompartments as multiscale contrast agents.

panels adapted with permission from: b, ref. 43, Springer Nature Ltd; d, ref. 44, American Chemical Society.

Fig. 3: Genetically encodable air-filled protein nanostructures as multimodality contrast agents.

panels adapted with permission from: ce, ref. 59, AAAS; f, ref. 61, Springer Nature Ltd; g, ref. 64, American Chemical Society.

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Acknowledgements

We are grateful to members of the Shapiro and Westmeyer laboratories for helpful discussions. Relevant research in the Shapiro laboratory was supported by the National Institutes of Health (grant nos. R01EB018975 and U54CA199090), the Human Frontier Science Program (RGP0050/2016), the Heritage Medical Research Institute, the Packard Foundation, the Pew Charitable Trust, the Sontag Foundation, the Dana Foundation and the Burroughs Wellcome Fund. A.F. was supported by an NSERC graduate fellowship. Relevant research in the Westmeyer laboratory was supported by the European Research Council under grant agreement nos. ERC-StG 311552 and ERC-COG 865710, the Deutsche Forschungsgemeinschaft through the TUM International Graduate School of Science and Engineering and the Federation of European Biochemical Societies.

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Farhadi, A., Sigmund, F., Westmeyer, G.G. et al. Genetically encodable materials for non-invasive biological imaging. Nat. Mater. 20, 585–592 (2021). https://doi.org/10.1038/s41563-020-00883-3

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