Genetically-engineered antivenom to improve the treatment of snake bite

Jun 27 2006

As reported in the latest issue of the prestigious medical journal, Public Library of Science: Medicine, researchers at the Liverpool School of Tropical Medicine have made an important breakthrough in using DNA sequencing rather than actual snake venom as the means to generate antivenom.

Antivenom is conventionally manufactured by immunising large animals with small quantities of venom and then extracting the antibodies produced in the blood. This new research has demonstrated however that it is possible to generate an antibody response by using synthetic DNA which closely resembles the most toxic and therefore the most important parts of actual venom.

Dr Simon Wagstaff and colleagues selected the carpet viper as the most medically important snake in west Africa. Using genetic techniques, they isolated the parts of the genes in the snake's venom gland which make the proteins responsible for the destruction of blood vessels and consequent haemorrhage, one of the often fatal outcomes of viper bites. They then identified seven parts of these proteins which were likely to be clinically important and synthesised them into a single DNA string for immunisation.

Immunisation with the DNA produced antibodies that reacted with many of the venom haemorrhagic toxins and also substantially neutralised their ability to cause haemorrhage.

The successful outcome of this "proof of principle" research has demonstrated that it is possible to use genetic techniques to produce immunogens (substances that generate an immune response in a host animal) to generate targeted antibodies for specific toxins.

Dr Rob Harrison, Head of the Alistair Reid Venom Research Unit at the School explained: "By raising antibodies against specific toxins rather than the whole venom (as in traditional antivenom production), this approach could offer significant improvements such as using lower doses of antivenoms which in turn reduces the risk of an adverse reaction which frequently occurs as a result of the large volumes of conventional antivenom that has to be given to cure the victim of the snake bite.

"However, it is important to stress that this research has only demonstrated the possibility of manufacturing antivenom in this way and only against a specific toxin group," he added. Further work is now underway to extend this research to other toxins.