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Organelle-level precision with next-generation targeting technologies

Nature Reviews Materials volume 7, pages 355–371 (2022)Cite this article

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Abstract

Intracellular organelles are subsystems within a cell, whose activity and chemical composition reflect the metabolic state of live cells. Alterations in cellular homeostasis occurring in disease, ageing and development are also reflected at the level of organelles. By targeting organelles with pharmacological agents and genetic tools, the aim is to improve disease diagnosis and to restore cell function. In this Review, we discuss biological pathways that can be exploited to target the delivery of exogenous cargo with organelle-level precision. We investigate how these pathways can be leveraged for imaging, diagnosis and therapy at the organelle level, and highlight the potential of nucleic acids as delivery systems to target specific organelles in vivo, including the nucleus, lysosomes, secretory organelles and mitochondria. The programmability, modularity and biocompatibility of nucleic acid-based scaffolds make them well suited to accomplishing next-generation targeting with organelle-level resolution in living organisms.

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Fig. 1: Organelles regulate intercellular communication.
Fig. 2: Exploiting biological pathways to access the nucleus and lysosome.
Fig. 3: Exploiting biological pathways to access secretory organelles and mitochondria.
Fig. 4: Nucleic acids for organelle-precision delivery.
Fig. 5: DNA nanodevices can be targeted to specific organelles.

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Acknowledgements

The authors thank Verenice Noyola for scientific illustrations. This work was supported by the Women’s Board of the University of Chicago; by grant number FA9550-19-0003 from AFOSR, by NIH grants R21NS114428 and 1R01NS112139-01A1, by the Mergel Funsky Award, by the Zhong Ziyi Educational Foundation Award and by the Ono Pharma Foundation.

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  1. These authors contributed equally: Anand Saminathan, Matthew Zajac.

Authors and Affiliations

  1. Department of Chemistry, The University of Chicago, Chicago, IL, USA

    Anand Saminathan, Matthew Zajac, Palapuravan Anees & Yamuna Krishnan

  2. Grossman Institute of Neuroscience, Quantitative Biology and Human Behaviour, The University of Chicago, Chicago, IL, USA

    Anand Saminathan, Matthew Zajac, Palapuravan Anees & Yamuna Krishnan

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A.S., M.Z., P.A. and Y.K. developed the review outline, wrote the manuscript and incorporated figures and references.

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Correspondence to Yamuna Krishnan.

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Y.K. is the co-founder and Chief Science Officer of Esya Inc., which uses DNA reporters. The other authors declare no competing interests.

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Saminathan, A., Zajac, M., Anees, P. et al. Organelle-level precision with next-generation targeting technologies. Nat Rev Mater 7, 355–371 (2022). https://doi.org/10.1038/s41578-021-00396-8

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