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

Allemann, Rudolf K. ORCID: https://orcid.org/0000-0002-1323-8830, Samperio, Raquel, Mart, Robert ORCID: https://orcid.org/0000-0003-2196-5840, Luk, Louis ORCID: https://orcid.org/0000-0002-7864-6261, Tsai, Yu-Hsuan ORCID: https://orcid.org/0000-0003-0589-5088, Jones, Arwyn ORCID: https://orcid.org/0000-0003-2781-8905 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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Abstract

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 Pharmacy
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
URI:	https://orca.cardiff.ac.uk/id/eprint/149246

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