Article (Scientific journals)
ADDovenom: Thermostable Protein-Based ADDomer Nanoparticles as New Therapeutics for Snakebite Envenoming
Menzies, Stefanie K.; Arinto-Garcia, Raquel; Gobbi Amorim, Fernanda et al.
2023In Toxins, 15 (12), p. 673
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Keywords :
Health, Toxicology and Mutagenesis; Toxicology
Abstract :
[en] Snakebite envenoming can be a life-threatening medical emergency that requires prompt medical intervention to neutralise the effects of venom toxins. Each year up to 138,000 people die from snakebites and threefold more victims suffer life-altering disabilities. The current treatment of snakebite relies solely on antivenom—polyclonal antibodies isolated from the plasma of hyperimmunised animals—which is associated with numerous deficiencies. The ADDovenom project seeks to deliver a novel snakebite therapy, through the use of an innovative protein-based scaffold as a next-generation antivenom. The ADDomer is a megadalton-sized, thermostable synthetic nanoparticle derived from the adenovirus penton base protein; it has 60 high-avidity binding sites to neutralise venom toxins. Here, we outline our experimental strategies to achieve this goal using state-of-the-art protein engineering, expression technology and mass spectrometry, as well as in vitro and in vivo venom neutralisation assays. We anticipate that the approaches described here will produce antivenom with unparalleled efficacy, safety and affordability.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Menzies, Stefanie K. ;  Centre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK ; Centre for Drugs & Diagnostics, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
Arinto-Garcia, Raquel ;  iBET, Instituto de Biologia Experimental e Technológica, Apartado 12, 2781-901 Oeiras, Portugal ; ITQB NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal
Gobbi Amorim, Fernanda  ;  Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
Cardoso, Iara Aimê ;  Centre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
Abada, Camille;  Centre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
Crasset, Thomas  ;  Université de Liège - ULiège > Faculté des Sciences > Master en sc. chimiques, à fin.
Durbesson, Fabien;  Architecture et Fonction des Macromolécules Biologiques, CNRS, Aix-Marseille Université, 13009 Marseille, France
Edge, Rebecca J.;  Centre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
El-Kazzi, Priscila;  Architecture et Fonction des Macromolécules Biologiques, CNRS, Aix-Marseille Université, 13009 Marseille, France
Hall, Sophie;  School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK ; Max Planck Bristol Centre for Minimal Biology, Cantock’s Close, Bristol BS8 1TS, UK
Redureau, Damien ;  Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
Stenner, Richard;  School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK ; Max Planck Bristol Centre for Minimal Biology, Cantock’s Close, Bristol BS8 1TS, UK
Boldrini-França, Johara;  School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK ; Max Planck Bristol Centre for Minimal Biology, Cantock’s Close, Bristol BS8 1TS, UK
Sun, Huan;  School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK ; Max Planck Bristol Centre for Minimal Biology, Cantock’s Close, Bristol BS8 1TS, UK
Roldão, António ;  iBET, Instituto de Biologia Experimental e Technológica, Apartado 12, 2781-901 Oeiras, Portugal ; ITQB NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal
Alves, Paula M. ;  iBET, Instituto de Biologia Experimental e Technológica, Apartado 12, 2781-901 Oeiras, Portugal ; ITQB NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal
Harrison, Robert A.;  Centre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK ; Centre for Drugs & Diagnostics, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
Vincentelli, Renaud ;  Architecture et Fonction des Macromolécules Biologiques, CNRS, Aix-Marseille Université, 13009 Marseille, France
Berger, Imre ;  School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK ; Max Planck Bristol Centre for Minimal Biology, Cantock’s Close, Bristol BS8 1TS, UK
Quinton, Loïc  ;  Université de Liège - ULiège > Département de chimie (sciences) > Chimie biologique
Casewell, Nicholas R. ;  Centre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK ; Centre for Drugs & Diagnostics, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
Schaffitzel, Christiane ;  School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK
More authors (12 more) Less
Language :
English
Title :
ADDovenom: Thermostable Protein-Based ADDomer Nanoparticles as New Therapeutics for Snakebite Envenoming
Publication date :
28 November 2023
Journal title :
Toxins
eISSN :
2072-6651
Publisher :
MDPI AG
Volume :
15
Issue :
12
Pages :
673
Peer reviewed :
Peer Reviewed verified by ORBi
European Projects :
H2020 - 899670 - ADDovenom - ADDovenom: Novel Snakebite Therapy Platform of Unparalleled Efficacy, Safety and Affordability
Funders :
EU - European Union [BE]
Funding text :
This work is supported by a Horizon 2020 FET OPEN grant ‘ADDovenom’ (899670).
Available on ORBi :
since 19 January 2024

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