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Nat Methods. 2016 Mar;13(3):263-8. doi: 10.1038/nmeth.3735. Epub 2016 Jan 25.

A genetically targetable near-infrared photosensitizer.

Author information

1
Department of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
2
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
3
Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
4
Center for Biologic Imaging, Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
5
Molecular Biosensor and Imaging Center, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.

Abstract

Upon illumination, photosensitizer molecules produce reactive oxygen species that can be used for functional manipulation of living cells, including protein inactivation, targeted-damage introduction and cellular ablation. Photosensitizers used to date have been either exogenous, resulting in delivery and removal challenges, or genetically encoded proteins that form or bind a native photosensitizing molecule, resulting in a constitutively active photosensitizer inside the cell. We describe a genetically encoded fluorogen-activating protein (FAP) that binds a heavy atom-substituted fluorogenic dye, forming an 'on-demand' activated photosensitizer that produces singlet oxygen and fluorescence when activated with near-infrared light. This targeted and activated photosensitizer (TAPs) approach enables protein inactivation, targeted cell killing and rapid targeted lineage ablation in living larval and adult zebrafish. The near-infrared excitation and emission of this FAP-TAPs provides a new spectral range for photosensitizer proteins that could be useful for imaging, manipulation and cellular ablation deep within living organisms.

PMID:
26808669
PMCID:
PMC4916159
DOI:
10.1038/nmeth.3735
[Indexed for MEDLINE]
Free PMC Article

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