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: | Schools > Chemistry Schools > 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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