Balforth, MR, Haigh, J orcid.org/0000-0002-9518-4003, Kumar, V et al. (6 more authors) (2021) Piggybacking on the Cholera Toxin: Identification of a CTB-binding Protein as an Approach for Targeted Delivery of Proteins to Motor Neurons. Bioconjugate Chemistry, 32 (10). pp. 2205-2212. ISSN 1043-1802
Abstract
A significant unmet need exists for the delivery of biologic drugs such as polypeptides or nucleic acids to the central nervous system for the treatment and understanding of neurodegenerative diseases. Naturally occurring bacterial toxins have been considered as tools to meet this need. However, due to the complexity of tethering macromolecular drugs to toxins and the inherent dangers of working with large quantities of recombinant toxins, no such route has been successfully exploited. Developing a method where a bacterial toxin’s nontoxic targeting subunit can be assembled with a drug immediately prior to in vivo administration has the potential to circumvent some of these issues. Using a phage-display screen, we identified two antibody mimetics, anticholera toxin Affimer (ACTA)-A2 and ACTA-C6 that noncovalently associate with the nonbinding face of the cholera toxin B-subunit. In a first step toward the development of a nonviral motor neuron drug-delivery vehicle, we show that Affimers can be selectively delivered to motor neurons in vivo.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 American Chemical Society. This is an author produced version of an article, published in Bioconjugate Chemistry. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Organic Chemistry (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Synthetic Biology (Leed) |
Funding Information: | Funder Grant number EU - European Union 746421 EU - European Union 814029 |
Depositing User: | Symplectic Publications |
Date Deposited: | 20 Sep 2021 12:37 |
Last Modified: | 27 Sep 2022 00:13 |
Status: | Published |
Publisher: | American Chemical Society |
Identification Number: | 10.1021/acs.bioconjchem.1c00373 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:178298 |