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Spatio-temporal control of cell death by selective delivery of photo-activatable proteins

Allemann, Rudolf K. ORCID:, Samperio, Raquel, Mart, Robert ORCID:, Luk, Louis ORCID:, Tsai, Yu-Hsuan ORCID:, Jones, Arwyn ORCID: and Cruz Samperio, Raquel 2022. Spatio-temporal control of cell death by selective delivery of photo-activatable proteins. ChemBioChem 23 (12) , e202200115. 10.1002/cbic.202200115

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Protein therapeutics offer exquisite selectivity in targeting cellular processes and behaviors, but are rarely used against non-cell surface targets due to their poor cellular uptake. While cell-penetrating peptides can be used to deliver recombinant proteins to the cytosol, it is generally difficult to selectively deliver active proteins to target cells. Here, we report a recombinantly produced, intracellular protein delivery and targeting platform that uses a photocaged intein to regulate the spatio-temporal activation of protein activity in selected cells upon irradiation with light. The platform was successfully demonstrated for two cytotoxic proteins to selectively kill cancer cells after photo-activation of intein splicing. This platform can generically be applied to any protein whose activity can be disrupted by a fused intein, allowing it to underpin a wide variety of future protein therapeutics.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Additional Information: This is an open access article under the terms of the Creative Commons Attribution License
Publisher: Wiley-VCH Verlag
ISSN: 1439-4227
Funders: BBSRC
Date of First Compliant Deposit: 20 April 2022
Date of Acceptance: 12 April 2022
Last Modified: 24 May 2023 23:10

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