TY - JOUR
T1 - ADDovenom
T2 - Thermostable Protein-Based ADDomer Nanoparticles as New Therapeutics for Snakebite Envenoming
AU - Menzies, Stefanie K.
AU - Arinto-Garcia, Raquel
AU - Amorim, Fernanda Gobbi
AU - Cardoso, Iara Aimê
AU - Abada, Camille
AU - Crasset, Thomas
AU - Durbesson, Fabien
AU - Edge, Rebecca J.
AU - El-Kazzi, Priscila
AU - Hall, Sophie
AU - Redureau, Damien
AU - Stenner, Richard
AU - Boldrini-França, Johara
AU - Sun, Huan
AU - Roldão, António
AU - Alves, Paula M.
AU - Harrison, Robert A.
AU - Vincentelli, Renaud
AU - Berger, Imre
AU - Quinton, Loïc
AU - Casewell, Nicholas R.
AU - Schaffitzel, Christiane
N1 - Funding Information:
This work is supported by a Horizon 2020 FET OPEN grant ‘ADDovenom’ (899670).
Publisher Copyright:
© 2023 by the authors.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - ADDomer
KW - antivenom
KW - biologics
KW - snakebite
KW - venom
UR - http://www.scopus.com/inward/record.url?scp=85180732967&partnerID=8YFLogxK
U2 - 10.3390/toxins15120673
DO - 10.3390/toxins15120673
M3 - Article
C2 - 38133177
AN - SCOPUS:85180732967
SN - 2072-6651
VL - 15
JO - Toxins
JF - Toxins
IS - 12
M1 - 673
ER -