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

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.

Venom diversity inNaja mossambica: Insights from proteomic and immunochemical analyses reveal intraspecific differences

“…In recent years, there has been an intensive search for alternatives to current therapeutic solutions following snakebites, including innovative approaches such as using recombinant antivenoms based on monoclonal antibodies, employing small molecules to inhibit the activity of certain enzymes, and utilizing virus-derived protein scaffold to neutralize venom toxins [27][28][29]. However, until new solutions are developed, snakebite treatments predominantly rely on the use of antivenoms obtained through the immunization of large domestic animals.…”