Mutating Enzymes to Stop Nerve Agents
Mutated enzymes that were able to detoxify the G-type nerve agent before the nerve agent reached the target and caused injury went on to further testing, and after four rounds of testing, Dr. Tawfik had PON1 variants that worked up to 340 times better at detoxifying the nerve agents. These PON1 variants are intended for use as an injection to military personnel to serve as a preventative and post-exposure treatment.
Why is this important? Dr. Tawfix explains:
“The primary goal in this study is a prophylactic measure, not post-expoure. The action of most nerve agents is so rapid that treatment after exposure is challenging. It’s likely that the damage can be minimized if these neutralizing enzymes are given immediately afterexposure, but we have not demonstrated that. I would also note that we are aiming at post-exposure treatment for exposure to other nerve agents that can penetrate through the skin (VX; that is neutralized by the engineered variants but not with high efficiency) and hence act slowly, and also pesticides. Indeed, we are now continuing the engineeering for effective VX neutralization.
Dr. Tawfix also told us that “Engineer variants for neutralization of the V-type agents (far more lethal, skin penetrating)” are the next step for this line of research.
The Powers of Enzyme Engineering
According to Dr. Tawfix, there are deeper implications than are immediately evident in the results of this study – he says,
Beyond the applications, this work demonstrates the powers of enzyme engineering – the ability to generate tailor-made enzymes whose catalytic proficiency and selectivity rival those of natural enzymes.
Dr. Tawfix’s work has advanced the protection of those who are at a high risk for being exposed to a chemical attack – our men and women on the front lines. This advance also provides scientists with a better understanding of how naturally-occurring enzymes work, and how they can be used to protect us from dangerous chemical attacks.
Goldsmith et al.: Evolved stereoselective hydrolases for broad-spectrum G-type nerve agent detoxification. (2012). Chemistry & Biology. Accessed April 18, 2012.
United States Department of Homeland Security. Chemical Attack Warfare Aagents, Industrial Chemicals, and Toxins. (2004). Accessed April 18, 2012.
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