Gene transfer of acetylcholinesterase protects the knockout mouse from the toxicity of DFP.

Acetylcholinesterase (AChE) has a clear role in nerve impulse transmission. Organophosphorus esters are highly toxic chemicals used as pesticides, fire retardants, plasticizers, and chemical warfare agents. The acute toxicity of organophosphorus poisons is attributed to inhibition of AChE in nerve synapses. This leads to seizures, respiratory arrest, and death. Our goal was to find a new therapeutic for protection against the toxicity of organophosphates (OPs). We investigated the feasibility of using a gene therapy vector to deliver AChE over long time periods and in quantities sufficiently high to provide protection against diisopropylfluorophosphate (DFP) toxicity. We used the AChE-/- mouse for these studies because this mouse has no endogenous AChE activity (Xie et al., 2000). Any AChE activity found in tissues could only come from the viral vector.