Preprint Communication Version 1 Preserved in Portico This version is not peer-reviewed

ADDovenom: Thermostable Protein-Based ADDomer Nanoparticles as New Therapeutics for Snakebite Envenoming

Version 1 : Received: 16 October 2023 / Approved: 17 October 2023 / Online: 17 October 2023 (11:13:01 CEST)

A peer-reviewed article of this Preprint also exists.

Menzies, S.K.; Arinto-Garcia, R.; Amorim, F.G.; Cardoso, I.A.; Abada, C.; Crasset, T.; Durbesson, F.; Edge, R.J.; El-Kazzi, P.; Hall, S.; Redureau, D.; Stenner, R.; Boldrini-França, J.; Sun, H.; Roldão, A.; Alves, P.M.; Harrison, R.A.; Vincentelli, R.; Berger, I.; Quinton, L.; Casewell, N.R.; Schaffitzel, C. ADDovenom: Thermostable Protein-Based ADDomer Nanoparticles as New Therapeutics for Snakebite Envenoming. Toxins 2023, 15, 673. Menzies, S.K.; Arinto-Garcia, R.; Amorim, F.G.; Cardoso, I.A.; Abada, C.; Crasset, T.; Durbesson, F.; Edge, R.J.; El-Kazzi, P.; Hall, S.; Redureau, D.; Stenner, R.; Boldrini-França, J.; Sun, H.; Roldão, A.; Alves, P.M.; Harrison, R.A.; Vincentelli, R.; Berger, I.; Quinton, L.; Casewell, N.R.; Schaffitzel, C. ADDovenom: Thermostable Protein-Based ADDomer Nanoparticles as New Therapeutics for Snakebite Envenoming. Toxins 2023, 15, 673.

Abstract

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 snakebite and 3-fold more victims suffer life-altering disabilities. 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 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 with 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, 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.

Keywords

snakebite; antivenom; venom; biologics; ADDomer

Subject

Biology and Life Sciences, Toxicology

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