Harnessing the natural potential of venom for drug discovery

Venoms, found in many species of reptiles, invertebrates and even fish, are commonly known for their ability to cause periods of severe pain and even paralysis. Paradoxically, the venom can also be used as a medicine to relieve pain.

Steven Trim, Founder and Scientific Director of Venomtech®tells NewsMedical how the UK-based company is harnessing the painkilling power of naturally produced venoms from a collection of nearly 200 species of spiders, scorpions and centipedes to create libraries of compounds for drug discovery.

Could you please give us an overview of Venomtech® and your role there?

I founded Venomtech® in 2010 to manufacture and supply venom peptides, primarily for drug discovery, and has now become a world leader in venom research ventures. We have a lab with over 200 venomous species, from which we collect venom and screen to identify useful compounds to manufacture.

These compounds can then be used in various industries, from pharmaceuticals to cosmetics, including the development of insecticides. Part of my role is to oversee the supply chain, including helping to set up and establish our laboratory, as well as finding reliable suppliers and optimizing production processes.

Image Credit: ShutterStock/Agus_Gatam

Which application areas benefit from Venom Libraries, and where Venomtech® Come in?

Our expertise is in drug discovery, which means our main markets are the pharmaceutical and biotechnology sectors – with some interest from academia – where venom-derived compounds lead to the discovery of new pain and oncology drugs.

We have also been involved in antimicrobial and epigenetic studies and during the recent lockdown the team even worked on SARS-CoV-2 interactions. In addition, we also serve a number of secondary markets, including the development of cosmetics and insecticides. For the pest control market, many spider venoms have evolved to kill insects, providing a good opportunity to use venoms in bio-based insecticides that do not bioaccumulate in soil and only target insects. pests, not pollinators.

In recent years, we have developed a soothing biomimetic peptide called SensAmone P5, which calms sensitive skin and reduces irritation by blocking pain receptors. We have also been involved in the development of a synthetic snake venom that is already used in Botox-like procedures, and several other products that will be released this year.

How do you go about creating an effective venom library or database?

Each species has its own unique venom containing several hundred different components. Therefore, the library of compounds available to us from venom is enormous, and we are only scratching the surface. In order for us to turn them into products, we must understand the activity of each venom and reproduce it in a synthetic product to ensure that we are not dependent on animals for the final version. To do this, we screen libraries of individual compounds to identify what they are, how effective they are for the chosen application, and how to make them synthetically. This process begins with splitting venom we collect using high performance liquid chromatography (HPLC) and then prepare assay-ready plates for screening.

Our key to success is Targeted-Venom Discovery Array™ (T-VDA). We built this to maximize the chance of success by focusing the right venoms on the right target. We typically build a T-VDA by splitting 12 venoms, but we also build larger libraries by splitting them into individual components.

To construct a T-VDA, each venom is fractionated by 2D HPLC, where two different chromatographic columns are connected in sequence to better resolve the individual fractions. Samples are then standardized, plated, and lyophilized in 384-well plates to create the compound library.

What challenges do you face and how do you adapt to working with different industries?

The biggest challenge to the efficiency of our workflow is that HPLC produces venom fractions in a 96-well format, and our customers in the drug discovery industry typically use 384-well plates as their format. standard.

Therefore, we needed a robust and reproducible method of transferring venoms from 96 to 384 well plate formats. Our team uses a VOYAGER Adjustable Tip Spacing Pipette from INTEGRA Biosciences to increase the efficiency of plate preparation for screening assays. This portable electronic pipette allows the user to adjust the spacing between each tip to easily transfer samples from one labware format to another.

Image credit: ShutterStock/Kurit Afshen

The main driver for our decision to choose the VOYAGER pipette was the ability to significantly improve our efficiency when pipetting 96 to 384 well plates. The INTEGRA VOYAGER pipette allows us to produce a 384 plate more efficiently than before.

Before owning the VOYAGER, we had to pipette each well one at a time to transfer samples and substrates to the correct plate format, which would take hours, but the VOYAGER allows us to do this in minutes. For us, the ability to adjust tip spacing electronically, and with one hand, are major advantages.

What benefits do you get by using the INTEGRA VOYAGER?

The VOYAGER is an incredible workhorse as it solves such an important problem in our lab by pipetting between different formats of labware. We use it for almost everything we do, including quality control, building our T-VDAs, and our own in-house research and development.

We love the VOYAGER for several reasons: it’s quiet, precise and lightweight, making it the ideal pipetting tool. The repeat dispense function is a really great feature, as it makes pipetting much more efficient, reducing the number of times you have to return to the reservoir. The serial dilution feature is also perfect for creating standards in a test plate.

Image Credit: ShutterStock/INTEGRA Biosciences

Another outstanding feature for working with INTEGRA was the GRIPTIPS pipette tips. The GRIPTIPS form a precise seal on the VOYAGER pipette, reducing the risk of tip dripping and giving us confidence that we are preparing precisely the right volume every time.

The VOYAGER also has a display with a dispense counter, which is very useful if you are disturbed – for example, if someone asks you a question – as it tells you where you are, so you can easily resume. where you left off. Plus, the user interface is simple, which means training is minimal, even for new staff.

We are also very satisfied with the INTEGRA service team. We bought our VOYAGER about seven years ago, and it only needed to be offsite once for maintenance, which is fantastic, especially considering how much it’s been used.

How important is having an affordable pipetting platform to support growth and R&D at Venomtech®?

As a small, nimble biotech company, we have to be careful where we invest our funds. But the VOYAGER was a major step up from manual pipetting, saving us a lot of time, and more than paying for it. The pipette is very intuitive, even if you are not used to using an electronic pipette, so the whole team – both new and experienced, including several of our visiting postgraduate students from the University Canterbury Christ Church nearby – can use with minimal training which will be invaluable as the business grows.

Image Credit: ShutterStock/DedeDian

I have worked in drug discovery for over 20 years and have used many manual and electronic pipettes. The VOYAGER far exceeds anything I’ve tried, not only for its capabilities, but also because of the high quality service and interactions we have with INTEGRA. It is today the only brand of electronic or multichannel pipette that we use.

About INTEGRA Biosciences

Moving liquids precisely and productively is at the heart of the work of many laboratory professionals in the life science industry. Since 1965, INTEGRA has been dedicated to the development of pipetting and media preparation solutions, meeting the needs of our customers in research, diagnostics and quality control. It’s our passion to work side-by-side with our customers to understand their issues and meet their needs with innovative products. To accomplish this, we maintain our own sales and support organizations in the United States, Canada, China, Japan, United Kingdom, Sweden, France, Germany, Austria and Switzerland, as well than a network of more than 100 highly qualified distribution partners worldwide.

INTEGRA’s engineering and production teams in Zizers, Switzerland and Hudson, NH, USA strive to develop and manufacture instruments and consumables of exceptional quality. In recent years we have focused on completing our range of technologically advanced liquid handling products, culminating in the launch of the D-ONE single channel pipetting module for the ASSIST PLUS robot; a revolutionary concept that combines state-of-the-art pipetting with state-of-the-art robotics, freeing scientists from routine pipetting. We are proud to offer the widest range of pipettes on the market, ranging from single-channel mechanical pipettes to 384-channel electronic benchtop platforms.

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