Project description
Proteomics, transcriptomics and bioinformatics for development of novel snakebite therapy
Snakebites can be life-threatening when venom toxins are injected and enter the bloodstream. In areas where immediate access to specialised medical care is limited, bites by venomous snakes cause many thousands of deaths each year. The EU-funded ADDovenom project will use an innovative platform enabling generation of new snakebite treatment, based on a new disruptive protein-based nanoscaffold called ADDomer – a megadalton-sized, thermostable synthetic virus-like particle with 60 high-affinity binding sites to neutralise and eliminate venom toxins from the bloodstream. ADDovenom combines pioneering proteomics, transcriptomics and bioinformatics focusing on snake toxins provoking the most challenging syndromes like haemorrhage and paralysis. The aim is to develop first-in-class neutralising superbinders for snakebite therapy of unprecedented efficacy against the most prevalent Sub-Saharan snakes.
Objective
ADDovenom initiates a major multidisciplinary effort to achieve a timely step-change in snakebite therapy, by creating an innovative platform with transformative potential for antivenom generation to save countless lives. ADDovenom exploits a disruptive new, protein-based nanoscaffold we developed, the ADDomer - a megadalton sized, thermostable synthetic virus-like particle that offers 60 high-affinity binding sites to rapidly eliminate venom toxins from the blood stream. Further, we will for the first time deploy ADDobody, a small, stable protein motif with randomized flexible loops that will be utilized as a naïve library to select and evolve high-affinity binders in vitro by Ribosome Display. Of note, the ADDobody and ADDomer ‘superbinder’ formats are interconvertible.
The ADDovenom project brings to bear cutting-edge proteomics, transcriptomics and bioinformatics to inventorise the toxin repertoire of eight snakes that inflict the most clinically-challenging envenoming syndromes in sub-Saharan Africa: haemorrhage, coagulopathy, paralysis and tissue necrosis. We will implement rational design and high-throughput expression to produce antigens for our selections, based on the major toxin groups we target. We will design consensus-toxins and epitope strings combining conserved sequences, to achieve maximal intergeneric efficacy of our ADDobody binders, boosting neutralizing efficacy for entire toxin families simultaneously. We will develop state-of-the-art bioprocessing to manufacture ADDomer-based antivenoms at pharma scale, preparing for future clinical trials.
To achieve these ambitious goals, ADDovenom synergistically combines unique expertise across a range of techniques and scientific disciplines, towards the objective to develop easy to produce, first-in-class neutralizing superbinders for snakebite therapy, to protect with unprecedented efficacy against the most prevalent snakebites – a strategy that can be adapted to all snakes in any geographic region.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
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Keywords
Programme(s)
Call for proposal
(opens in new window) H2020-FETOPEN-2018-2020
See other projects for this callSub call
H2020-FETOPEN-2018-2019-2020-01
Funding Scheme
RIA - Research and Innovation actionCoordinator
BS8 1QU Bristol
United Kingdom