Harnessing the natural potential of venom for drug discovery

insights from industrySteven TrimCheif Scientific Officer

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

Steven Trim, Founder and Chief Scientific Officer of Venomtech®, tells NewsMedical how the UK-based company harnesses the pain-relieving power of naturally-produced venoms from a collection of nearly 200 species of spiders, scorpions, and centipedes to create compound libraries for drug discovery.

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

I founded Venomtech® in 2010 to manufacture and supply venom peptides, principally for drug discovery, and it has now developed into a global leader in venom research enterprises. We have a laboratory containing over 200 venomous species, which we collect venom from and screen to identify useful compounds to manufacture.

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

Image Credit: ShutterStock/Agus_Gatam

What application areas benefit from venom libraries, and where does Venomtech® come in?

Our expertise is in drug discovery, which means that our primary markets are the pharmaceutical and biotech sectors – with some interest from academia – where venom-derived compounds are driving the discovery of new pain relief 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 cosmetic products and insecticides. For the pest control market, many spider venoms have evolved to kill insects, providing a good opportunity to use venoms in biologically-derived insecticides that do not bioaccumulate in the soil, and only target pest insects, 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 developing a synthetic snake venom that is already used in Botox-type procedures, and several more products that will be coming out 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 just scratching the surface. For us to manufacture these into products, we need to understand the activity of each venom, and replicate this in a synthetic product to ensure that we are not reliant on the animals for the final version. We do this by screening 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 fractioning the venom we collect using high-performance liquid chromatography (HPLC), then preparing assay-ready plates for screening.

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

To build 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 out, and freeze-dried in 384 well plates to create the compound library.

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

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

Therefore, we needed a robust and reproducible method of transferring the venoms from 96 to 384 well plates formats. Our team uses a VOYAGER adjustable tip spacing pipette from INTEGRA Biosciences to increase the efficiency of plate preparation for screening assays. This electronic handheld pipette enables 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 in our decision to select the VOYAGER pipette was the ability to greatly improve our efficiency when we are pipetting from 96 to 384 well plates. INTEGRA's VOYAGER pipette allows us to produce a 384 plate more efficiently than we could before.

Prior to owning the VOYAGER, we would have to pipette each well one by one to transfer samples and substrates into the correct plate format, which would take hours, but the VOYAGER allows us to do it in minutes. For us, the ability to adjust the tip spacing electronically, and with one hand, are major benefits.

What advantages do you get when using INTEGRA’s VOYAGER?

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

There are a number of reasons why we love the VOYAGER: it is quiet, precise, and lightweight, making it the ideal pipetting tool. The repeat dispense function is a really important feature, because it makes pipetting much more efficient, reducing the number of times that you have to go back to the reservoir. The serial dilution function is also perfect for creating standards in an assay plate.

Image Credit: ShutterStock/INTEGRA Biosciences

The GRIPTIPS pipette tips were another real standout feature for working with INTEGRA. The GRIPTIPS form a precise seal on the VOYAGER pipette, reducing the risk of dripping tips, and giving us the confidence that we are accurately preparing the correct volume every time.

The VOYAGER also has a display with a dispensing counter, which is really helpful if you get disrupted – for example, if somebody asks you a question – as it tells you where you are, so you can easily pick up where you left off. In addition, the user interface is straightforward, meaning that training is minimal, even for new members of staff.

We are also really pleased with the service team from INTEGRA. We bought our VOYAGER around seven years ago, and it has only had to go off-site for servicing once, which is fantastic, especially considering how much use it gets.

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

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

Image Credit: ShutterStock/DedeDian

I have worked in drug discovery for over 20 years, and used many manual and electronic pipettes. The VOYAGER stands head and shoulders above anything else I have tried, not only for its capabilities, but also thanks to the high-quality service and interactions that we have with INTEGRA. It is now the only brand of electronic or multichannel pipette that we use.

About INTEGRA Biosciences

Moving liquids in a precise and productive way is core to the work of many laboratory professionals in the life sciences industry. Since 1965, INTEGRA has been dedicated to developing solutions for pipetting and media preparation, fulfilling the needs of our customers in research, diagnostics and quality control. It is our passion to work side by side with our customers to understand their problems and meet their needs with innovative products. In order to do this, we maintain our own sales and support organizations in the USA, Canada, China, Japan, UK, Sweden, France, Germany, Austria and Switzerland, as well as a network of over 100 highly trained 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 outstanding quality. In recent years, we have focused on completing our technologically advanced liquid handling product range, 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 cutting edge robotics, freeing scientists from routine pipetting. We are proud to offer the widest product line of pipettes in the market, spanning from single channel mechanical pipettes up to 384 channel electronic benchtop platforms.


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