The Use of Plant-Derived Ribosome Inactivating Proteins in Immunotoxin Development: Past, Present and Future Generations

Ribosome inactivating proteins (RIPs) form a class of toxins that was identified over a century ago. They continue to fascinate scientists and the public due to their very high activity and long-term stability which might find useful applications in the therapeutic killing of unwanted cells but can...

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Main Authors: Aleksander Rust, Lynda J. Partridge, Bazbek Davletov, Guillaume M. Hautbergue
Format: Article
Language:English
Published: MDPI AG 2017-10-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/9/11/344
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author Aleksander Rust
Lynda J. Partridge
Bazbek Davletov
Guillaume M. Hautbergue
author_facet Aleksander Rust
Lynda J. Partridge
Bazbek Davletov
Guillaume M. Hautbergue
author_sort Aleksander Rust
collection DOAJ
description Ribosome inactivating proteins (RIPs) form a class of toxins that was identified over a century ago. They continue to fascinate scientists and the public due to their very high activity and long-term stability which might find useful applications in the therapeutic killing of unwanted cells but can also be used in acts of terror. We will focus our review on the canonical plant-derived RIPs which display ribosomal RNA N-glycosidase activity and irreversibly inhibit protein synthesis by cleaving the 28S ribosomal RNA of the large 60S subunit of eukaryotic ribosomes. We will place particular emphasis on therapeutic applications and the generation of immunotoxins by coupling antibodies to RIPs in an attempt to target specific cells. Several generations of immunotoxins have been developed and we will review their optimisation as well as their use and limitations in pre-clinical and clinical trials. Finally, we endeavour to provide a perspective on potential future developments for the therapeutic use of immunotoxins.
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spelling doaj.art-5a275e4b0ccb4b339210f67b713ae4dd2022-12-22T03:59:20ZengMDPI AGToxins2072-66512017-10-0191134410.3390/toxins9110344toxins9110344The Use of Plant-Derived Ribosome Inactivating Proteins in Immunotoxin Development: Past, Present and Future GenerationsAleksander Rust0Lynda J. Partridge1Bazbek Davletov2Guillaume M. Hautbergue3Structural and Molecular Biology, Division of Biosciences, Faculty of Life Sciences, University College London, London WC1E 6BT, UKDepartment of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UKDepartment of Biomedical Science, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UKSheffield Institute for Translational Neuroscience, Department of Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield S10 2HQ, UKRibosome inactivating proteins (RIPs) form a class of toxins that was identified over a century ago. They continue to fascinate scientists and the public due to their very high activity and long-term stability which might find useful applications in the therapeutic killing of unwanted cells but can also be used in acts of terror. We will focus our review on the canonical plant-derived RIPs which display ribosomal RNA N-glycosidase activity and irreversibly inhibit protein synthesis by cleaving the 28S ribosomal RNA of the large 60S subunit of eukaryotic ribosomes. We will place particular emphasis on therapeutic applications and the generation of immunotoxins by coupling antibodies to RIPs in an attempt to target specific cells. Several generations of immunotoxins have been developed and we will review their optimisation as well as their use and limitations in pre-clinical and clinical trials. Finally, we endeavour to provide a perspective on potential future developments for the therapeutic use of immunotoxins.https://www.mdpi.com/2072-6651/9/11/344ribosome inactivating proteinsimmunotoxinstherapeutic applications
spellingShingle Aleksander Rust
Lynda J. Partridge
Bazbek Davletov
Guillaume M. Hautbergue
The Use of Plant-Derived Ribosome Inactivating Proteins in Immunotoxin Development: Past, Present and Future Generations
Toxins
ribosome inactivating proteins
immunotoxins
therapeutic applications
title The Use of Plant-Derived Ribosome Inactivating Proteins in Immunotoxin Development: Past, Present and Future Generations
title_full The Use of Plant-Derived Ribosome Inactivating Proteins in Immunotoxin Development: Past, Present and Future Generations
title_fullStr The Use of Plant-Derived Ribosome Inactivating Proteins in Immunotoxin Development: Past, Present and Future Generations
title_full_unstemmed The Use of Plant-Derived Ribosome Inactivating Proteins in Immunotoxin Development: Past, Present and Future Generations
title_short The Use of Plant-Derived Ribosome Inactivating Proteins in Immunotoxin Development: Past, Present and Future Generations
title_sort use of plant derived ribosome inactivating proteins in immunotoxin development past present and future generations
topic ribosome inactivating proteins
immunotoxins
therapeutic applications
url https://www.mdpi.com/2072-6651/9/11/344
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