Spatio-Temporal Photoactivation of Cytotoxic Proteins |
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Authors: | Dr Raquel Cruz-Samperio Dr Robert J Mart Dr Louis Y P Luk Dr Yu-Hsuan Tsai Prof Arwyn T Jones Prof Rudolf K Allemann |
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Affiliation: | 1. School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT U.K.;2. Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edwards VII Ave, Cardiff, CF10 3NB U.K. |
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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 photoactivation 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. |
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Keywords: | barnase light-activation inteins photocaging saporin |
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