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The VENOMICS project is a four-year European project funded by the European Commission (EC) under the 7th Framework Program (HEALTH 2011-2015). It is conducted by a consortium of eight academic and industrial partners from five countries (France, Belgium, Spain, Portugal, Denmark), and benefits from a budget of six million Euros.

The project central goal is to exploit compounds originating from animal venoms for the development of novel therapeutics, by reproducing in vitro the molecular complexity of animal venoms.

Project participants will take advantage of the most recent technological developments in the fields of Next-Generation Sequencing (NGS), de novo peptide sequencing by mass spectrometry, peptide chemical synthesis and recombinant peptide production for high-throughput analysis of venom diversity.

Background

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Venoms are complex cocktails comprised of up to 1000 molecules, most of them being miniproteins called peptides. These peptides target the nervous, cardiovascular or muscular systems to cause paralysis and death of the prey. But it has also been shown that in the context of human diseases, the biological properties of venom peptides can be beneficial and that venom peptides can be useful per se or as templates for the design of novel drugs.[1][2] Several drugs derived from snake venom (Captopril®, Eptifibatide®, Tirofiban®) have been developed for the treatment of cardiovascular conditions, while a peptide from cone snail venom (Prialt®) is used to treat severe pain.[3][4] Another peptide from toxic lizard saliva (Byetta®) is commercialized for the treatment of type II diabetes.[5]

As there are more than 173,000 species of venomous animals, altogether venoms represent a “reservoir” of more than 40 million peptides with therapeutic potential.[6] But the exploration of this massive biodiversity represents a major scientific challenge, due to the size of the resource, scarcity of starting materials and the molecular complexity of venoms. To date, only 3000 to 4000 toxins have been described, and for most of them, pharmacological properties are either unknown or poorly characterized.

Project goals

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In order to address the problem of complexity and explore the molecular potential of venoms on a scale appropriate to the size of the resource, the VENOMICS project proposes the implementation of a new analytical paradigm, involving a combination of “-omics” technologies, followed by high-throughput production of venom peptides prior to investigation of their properties.[7][8]

Using a biobank of more than 500 venom samples and venom glands from various animal groups encompassing a broad range of biodiversity (insects, arachnids, snakes, sea anemones, etc.), high-throughput transcriptomics and proteomics techniques will be used to sequence and characterize more than 50,000 venom peptides from 200 animal species. Data will be stored in a dedicated database and used for selection of candidates for production. 10,000 peptides will be produced in vitro by Solid-Phase Peptide Synthesis (SPPS) and recombinant expression in Escherischia coli to build a peptide bank. This bank will subsequently be used for pharmacological screening and identification of promising drug leads.

Project management

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The VENOMICS project work has been subdivided into nine Work Packages (WP):

  • WP1 COORDINATION OF SCIENTIFIC AND TECHNICAL STRATEGY
  • WP2 BIOBANKS AND SOURCING: This WP is dedicated to collection of venomous specimen through sourcing missions in European countries of French overseas territories.
  • WP3 PROTEOMICS: WP3 includes the implementation of novel peptide sequencing methods by mass spectrometry and development of specific software for data interpretation.
  • WP4 TRANSCRIPTOMICS: In WP4, NGS technologies will be used to sequence venom gland transcriptomes and analyze data on a large scale.
  • WP5 PRODUCTION: In WP5, implementation of high-throughput peptide production will be based on two complementary approaches:
    • Optimization of methods for large scale recombinant peptide production in E. coli
    • Improvement of SPPS techniques and peptide refolding
  • WP6 VENOMICSERVER DATABASE: WP6 is devoted to the construction of a database that will centralize peptide sequences and data related to peptide characterization and screening.
  • WP7 PEPTIDE BANK: A 10,000 peptide bank will be produced in WP7. This WP also includes screening of the bank for identification of drug leads.
  • WP8 COMMUNICATION AND DISSEMINATION OF RESULTS, IP MANAGEMENT, BUSINESS DEVELOPMENT
  • WP9 PROJECT MANAGEMENT

Partners

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Partner Country Function
VenomeTech France Promoter and scientific coordinator of the project. Leader in venom-derived drug discovery.
CEA Saclay France Financial coordinator. Leader in peptide synthesis.
Université de la Méditerranée France Leader in high-throughput protein production.
Vitamib France Project management.
Université de Liège Belgium Leader in proteomics analysis.
Sistemas Genómicos Spain Leader in transcriptomics analysis.
NZYTech Portugal Leader in molecular biology.
Zealand Pharma Denmark Leader in drug development.

References

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  1. ^ Lewis, R.J. and M.L. Garcia, Therapeutic potential of venom peptides. Nature reviews. Drug discovery, 2003. 2(10): p. 790-802
  2. ^ King, G.F., Venoms as a platform for human drugs: translating toxins into therapeutics. Expert opinion on biological therapy, 2011. 11(11): p. 1469-84
  3. ^ Koh, C.Y. and R.M. Kini, From snake venom toxins to therapeutics--cardiovascular examples. Toxicon : official journal of the International Society on Toxinology, 2012. 59(4): p. 497-506
  4. ^ Miljanich, G.P., Ziconotide: neuronal calcium channel blocker for treating severe chronic pain. Current medicinal chemistry, 2004. 11(23): p. 3029-40
  5. ^ Giannoukakis, N., Exenatide. Amylin/Eli Lilly. Current opinion in investigational drugs, 2003. 4(4): p. 459-65
  6. ^ Lewis, R.J. and M.L. Garcia, Therapeutic potential of venom peptides. Nature reviews. Drug discovery, 2003. 2(10): p. 790-802
  7. ^ Vetter, I., et al., Venomics: a new paradigm for natural products-based drug discovery. Amino acids, 2011. 40(1): p. 15-28
  8. ^ Escoubas, P. and G.F. King, Venomics as a drug discovery platform. Expert review of proteomics, 2009. 6(3): p. 221-4.
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Category:European Commission projects Category:Toxins Category:Drugs Category:DNA sequencing Category:Proteomics Category:Peptides Category:Venomous animals Category:Omics Category:Biobanks Category:Drug discovery

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