VENOMICS

High-throughput peptidomics and transcriptomics of animal venoms for discovery of novel therapeutic peptides and innovative drug development

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 Obiettivo del progetto (Objective)

'Animal venoms are complex cocktails of peptides that have enormous potential as novel therapeutic leads. Replicating in vitro the diversity of venoms by generating large synthetic combinatorial peptide libraries will solve the challenge of working with limited amounts of natural products and permit high-throughput investigation of their pharmacology. A new investigation paradigm associating transcriptomics and proteomics is the only way to achieve this goal and to address the complexity of this unexplored 40,000,000 peptide resource. The vision of the VENOMICS project is to develop, integrate and implement cutting-edge and innovative technologies in a high-throughput approach to investigate the enormous structural and pharmacological diversity of venom peptides. We will use the largest venom and venom gland collection in the world to generate a comprehensive sequence database of bioactive peptides, and produce a 10,000 reticulated peptide bank to be used in drug discovery efforts and development of novel therapeutics. A 1000-fold improvement in throughput over the current situation (1 to 2 candidates generated per year) is reasonably foreseen. Implementation of the project will require both improvements and the integration of exisiting technologies in a high-throughput workflow comprising venom and tissue sourcing, mass spectrometry-based automated de novo peptide sequencing, transcriptomics of venom gland-derived RNA or cDNA/EST libraries, bioinformatics, implementation of a sequence database, and highly parallel synthetic or recombinant production including peptide refolding. The last step will be the validation of the approach in functional assays targeting specific pathologies. VENOMICS is a high-impact project with societal (new drugs against life threatening diseases), scientific and technological (filling the drug discovery pipeline), political (European leadership in the field) and economic (new opportunities for the biologics market) benefits.'

Introduzione (Teaser)

Discovering innovative medications from venoms is the vision of an EU-funded project. To this end, scientists are following an innovative process of venom characterisation and toxins production compatible with HTS.

Descrizione progetto (Article)

Spiders, scorpions, insects as well as some marine animals have the capacity to produce venoms. Given their high and complex content of peptides, venoms are increasingly being considered for their potential therapeutic use. Commercially available drugs already exist for alleviating pain in HIV and blood coagulation and are mostly based on snake and cone venom peptides. Currently, the pharmaceutical industry is investing more and more in venom-based drugs.

To study the diversity and pharmacology of venom peptides, scientists on the EU-funded VENOMICS project propose to generate the largest synthetic peptide library. To address the challenge of investigating part of the 170 000 venomous animals, consortium partners are combining proteomics, performed on venoms, and transcriptomics, performed on venom glands, extracted from 200 species.

They are generating a high-throughput workflow based on the largest collection of venom and tissue samples ever studied. The idea is to identify all the toxins expressed in venom glands and characterise peptide maturation occurring in the venom. In turn, this will allow the generation of 50 000 toxin sequences. From these, the 5 000 most interesting will be produced by chemical synthesis or recombinant expression.

Validation of both the approach and the selected peptides as drug candidates will be performed in functional and receptor-targeted assays specifically linked to age-related pathologies.

VENOMICS project open a new avenue in venoms exploration and exploitation with the development of unique technologies without any limitation issues associated with the availability of natural products.

The study is being performed at a scale never attempted before, and the generated libraries will feed into the drug pipeline. Overall, the VENOMICS drug discovery approach could offer innovative drugs as novel treatments for several medical conditions.