12th January 2013

New biotechnology could protect against deadly chemicals

An enzyme treatment which could neutralise the effects of lethal chemicals responsible for the deaths of hundreds of thousands of people across the world has been developed by experts at the University of Sheffield.

Organo-phosphorus agents (OP) are used as pesticides in developing countries, where acute poisoning is common because of insufficient control, poor storage, ready availability, and inadequate education amongst farmers. Globally an estimated 200,000 people die each year from OP poisoning, through occupational exposure, unintentional use and misuse – along with deliberate terrorist activities. OPs include compounds like Tabun (developed in 1936 by German scientists during WWII), Sarin, Soman, Cyclosarin, VX and VR.

In sub-Saharan Africa, the potential cost of pesticide-related illnesses between 2005 and 2020 could reach $90bn (£56bn) according to a UN report issued last year. This would exceed the total amount of international aid for basic health services in the region, excluding HIV/Aids. It is also a particular problem in India, Pakistan and Sri Lanka.

Using a modified human enzyme, Professor Mike Blackburn from the University of Sheffield’s Department of Molecular Biology and Biotechnology worked with Professor Alexander Gabibov of the Shemyakin-Ovchinnikov Institute, Moscow, and Professor Patrick Masson of the Centre de Recherches du Service de Santé des Armées, to create a “bioscavenger”, which was found to protect mice against the nerve agent VR and showed no lasting effects.

In studies performed at the Institute of Bioorganic Chemistry in Pushchino, Russia, a total of eight mice were treated with the new enzyme after being subjected to enough VR agent to kill several of the animals – 63 mg – and all survived.

Professor Blackburn said: “This current publication describes a novel method to generate a bioscavenger for the Russian VR organo-phosphorus agent with the key property of being long-acting in the bloodstream. That has been achieved by a combination of chemical surface modification (polysialylation) and biotechnology of production (through the use of an in vitro CHO-based expression system, employing genes encoding butyrylcholinesterase and a proline-rich peptide under special promoter control)."

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