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

Stefanie Menzies (1) , Raquel Arinto-Garcia , Fernanda Gobbi Amorim , Iara Aimê Cardoso (1) , Camille Abada , Thomas Crasset , Fabien Durbesson , Rebecca Edge , Priscila El-Kazzi , Sophie Hall , Damien Redureau , Richard Stenner , Johara Boldrini-França , Huan Sun , António Roldão , Paula Alves , Robert Harrison , Renaud Vincentelli (2) , Imre Berger , Loïc Quinton , Nicholas Casewell , Christiane Schaffitzel

1 LSTM - Liverpool School of Tropical Medicine
2 AFMB - Architecture et fonction des macromolécules biologiques

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.

Mots clés: snakebite; antivenom; venom; biologics; ADDomer

Domaines: Sciences du Vivant [q-bio]

Stefanie Menzies, Raquel Arinto-Garcia, Fernanda Gobbi Amorim, Iara Aimê Cardoso, Camille Abada, et al.. ADDovenom: Thermostable Protein-Based ADDomer Nanoparticles as New Therapeutics for Snakebite Envenoming. Toxins, 2023, 15 (12), pp.673. ⟨10.3390/toxins15120673⟩. ⟨hal-04382364⟩