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Published August 2016 | Accepted Version
Journal Article Open

Extracting structural and functional features of widely distributed biological circuits with single cell resolution via tissue clearing and delivery vectors


The scientific community has learned a great deal from imaging small and naturally transparent organisms such as nematodes and zebrafish. The consequences of genetic mutations on their organ development and survival can be visualized easily and with high-throughput at the organism-wide scale. In contrast, three-dimensional information is less accessible in mammalian subjects because the heterogeneity of light-scattering tissue elements renders their organs opaque. Likewise, genetically labeling desired circuits across mammalian bodies is prohibitively slow and costly via the transgenic route. Emerging breakthroughs in viral vector engineering, genome editing tools, and tissue clearing can render larger opaque organisms genetically tractable and transparent for whole-organ cell phenotyping, tract tracing and imaging at depth.

Additional Information

© 2016 Elsevier Ltd. We thank members of the Long Cai, Viviana Gradinaru, Dianne Newman, and Changhuei Yang groups at Caltech for useful discussions. Dr. Gradinaru is a Heritage Principal Investigator supported by the Heritage Medical Research Institute and a Pew Scholar in the Biomedical Sciences, supported by the Pew Charitable Trusts. This work was funded by grants to VG: the NIH Director's New Innovator IDP20D017782-01, PECASE, and NIH/NIA 1R01AG047664-01; as well as by funding support from the Beckman Institute for the Resource Center on CLARITY, Optogenetics, and Vector Engineering for technology development and broad dissemination (http://www.beckmaninstitute.caltech.edu/clover.shtml). California Institute of Technology filed intellectual property for some of the technologies described with authors as inventors.

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Accepted Version - nihms801239.pdf


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August 20, 2023
October 20, 2023