Catalytic Bioscavengers: The New Generation of Bioscavenger-Based Medical Countermeasures

The use of bioscavengers of organophosphorus agents (OPs) is the most effective alternative approach for neutralization or detoxification of OPs for decontamination under mild conditions, pretreatment, and postexposure treatment of poisoning by nerve agents (NAs). First-generation bioscavengers are stoichiometric scavengers. Among them, human butyrylcholinesterase (BChE) has been proven to be safe and effective for protection against poisoning by OP agents. However, stoichiometric neutralization of OPs needs the administration of huge amounts of costly biopharmaceuticals. Introduction of catalytic bioscavengers in medical countermeasures to OP poisoning will be a considerable improvement. Catalytic bioscavengers are enzymes capable of binding and detoxifying OPs with a turnover. Administered enzymes degrade toxic molecules before they reach their biological targets, thus providing protection against poisoning. Catalytic bioscavengers could also be used as active components in topical skin protectants (TSPs) and for decontamination of skin, mucosa, and wounds under mild conditions. The most promising enzymes are engineered mutants of paraoxonase. However, other phosphotriesterases (PTEs), prolidases and oxidases, catalytic antibodies, and engineered cholinesterases and carboxylesterases from various sources could be used. Certain secondary biological targets of OPs are also potential catalytic bioscavengers, particularly serum albumin, which reacts with OPs and self-reactivates. The implementation of strategies and methods of protein engineering allows large-scale production of enzymes displaying improved catalytic properties and that are not susceptible to inducing iatrogenic effects. Research regarding making immunologically compatible formulations stable in the bloodstream and during storage is another field of investigation.