Use of an Erythrocyte Platform to Deploy Technology for Infection Detection
Final rept. 12 Mar 1998-30 Sept 2001
BOSTON UNIV MA BIOMEDICAL ENGINEERING
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The goal of this initiative was to demonstrate the feasibility of deploying enzymatic tools within the vascular space for the purposes of detecting and disarming chemical and biological agents. The research succeeded in utilizing the red blood cell membrane surface as a platform on which to deploy an enzymatic defense system. The initial emphasis was changed from detection to protection because the molecular tools suitable for protection were immediately available. The project demonstrated that the intravascular platform provided by the red cell membrane and the strategy of enzymatic dismantling of a chemical threat agent were successful to a striking degree. The success included protection against a 20 fold lethal dose of paraoxone that was rendered totally innocuous with this strategy in less than 1 minute. Moreover, covalent attachment to the red cell surface provided such levels of protection for more than 3 days, in contrast to the rapid disappearance within 3 hours of protectant molecular tools that were not so immobilized. The detection aspect of the proposed project was placed second in priority to the protection aspect, but was in principle demonstrated by the protection experiments. We still needed the additional step of generating a signal for the cleaved chemical agent which could be amplified by the principles utilized for enzyme coupled immunoassays to generate detectable gustatory or olfactory signals in urine or plasma. The strategy proved totally unobtrusive and strikingly effective in dismantling threat agents. More time was required for further development of the detection strategies.
- Chemical, Biological and Radiological Warfare