Piggybacking on the Cholera Toxin: Identification of a CTB-Binding Protein as an Approach for Targeted Delivery of Proteins to Motor Neurons
| Autor: | Wenyue Dai, Christian Tiede, W. Bruce Turnbull, Michael E. Webb, Vajinder Kumar, Matthew R Balmforth, Jessica L Haigh, Jim Deuchars, Darren C. Tomlinson |
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| Rok vydání: | 2021 |
| Předmět: |
Cholera Toxin
Affimer Protein subunit Bacterial Toxins Biomedical Engineering Pharmaceutical Science Immunoglobulins Bioengineering medicine.disease_cause law.invention 03 medical and health sciences 0302 clinical medicine In vivo law medicine 030304 developmental biology Pharmacology Motor Neurons 0303 health sciences Toxin Chemistry Binding protein Organic Chemistry Cholera toxin Motor neuron 3. Good health Cell biology medicine.anatomical_structure Recombinant DNA Peptides 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | Bioconjugate chemistry. 32(10) |
| ISSN: | 1520-4812 1043-1802 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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