Brightfield microscopy image of snake venom gland organoid culture. Credits: Yorick Post, Joep Beumer, Jens Puschhof, Copyright Hubrecht Institute.

9 February 2021

DIY: how to develop venom-producing snake organoids

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Researchers from the group of Hans Clevers published a step-by-step protocol for the development and maintenance of snake venom gland organoids in the lab. Additionally, they share protocols for several applications, including the genetic engineering of such organoids and the collection of their venom. The methods that are explained in the protocol can potentially facilitate both the production of antivenom and the development of new venom-based drugs. The protocol was published in Nature Protocols on the 27th of January and is based on work in an international collaboration with the groups of Michael Richardson, Nicholas Casewell and Freek Vonk.

Bites from venomous snakes kill 100.000 and disable 400.000 people each year. However, snake venom is also a rich source of toxins that can be used for new therapeutics. Manually ‘milking’ snakes is currently the most common method to obtain snake venom but researchers from the Hubrecht Institute developed a safer method: they were able to grow organoids from the venom glands of snakes in the lab. The results were published in Cell last year. The tiny 3D organoid models mimic the function of actual snake venom glands, including the production of venom.

Brightfield microscopy image of snake venom gland organoid culture
Brightfield microscopy image of snake venom gland organoid culture. Credits: Yorick Post, Joep Beumer, Jens Puschhof, Copyright Hubrecht Institute.
Share with research community

Now, the researchers also published a step-by-step protocol for the development of such organoids, enabling the entire scientific community to use the technology to their advantage. “There are many snake-related research questions that are currently hard to address and we really feel that organoid technology can help to answer these important questions,” says Jens Puschhof, first author of the publication together with Yorick Post and Joep Beumer. With the protocol, researchers worldwide can start to grow and maintain snake venom gland organoids, genetically engineer them, harvest their venom and much more.

Fluorescent microscopy image of snake venom gland organoid with a king cobra
Fluorescent microscopy image of snake venom gland organoid with a king cobra. Credit fluorescent image: Ravian van Ineveld and Anne Rios, copyright Princess Maxima Center for Children's Oncology; Credit snake photo: Freek Vonk, copyright Naturalis.
Production of anti-venom

The venom produced by the snake organoids can be used for the production of anti-venom and the development of new venom-based drugs. Additionally, the researchers expect that the technology can also be used to grow organoids from other vertebrate animals, such as lizards or fish. “Hopefully, the many applications of our technology can advance human healthcare and reduce the devastating impact of snakebite in the future,” Puschhof concludes.

Publication

Puschhof, J., Post, Y., Beumer, J. et al. Derivation of snake venom gland organoids for in vitro venom production. Nature Protocols (2021).

Picture Hans Clevers

 

Hans Clevers is group leader at the Hubrecht Institute and the Princess Máxima Center for Pediatric Oncology, professor of Molecular Genetics at Utrecht University, and Oncode Investigator.