Development of Bioscavengers for U.S. Army

The U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) is seeking services to develop rapidly absorbed and persistent bioscavengers.

Bioscavengers are proteins that react specifically and quickly with organophosphate (OP) chemical agents without causing undesirable side-effects.

Medical chemical mitigation by bioscavengers is a promising means of protection against nerve agent toxicity. Two of the important desirable bioscavenger characteristics include rapid absorption of bioscavengers from an IM dose into the blood stream and persistence of this bioscavenger in the blood.

Under the proposed contract, USAMRICD wants to make use of mouse red blood cell (RBC) epitopes to target bioscavengers to RBCs. Therapeutic proteins delivered in this manner could potentially improve the retention times as great as the native RBC of 120 days. With such treatment it would be possible to retain higher effective concentrations of the therapeutic proteins and reduce or eliminate multiple dosing.

The means of the work will be to create an immunized domain Nb library by immunizing a llama or camel with the target protein ECD and mouse RBCs. RNA is extracted from splenocytes (or lymphocytes) and by PCR methods amplified and the VHH regions cloned into filamentous bacteriophages to produce a protein display library. The library is initially screened to isolate binders. The select library is then screened to identify high-affinity single domain binders. The identified high-affinity Nb genes will then be sequenced.

Further details are available under Solicitation Number: W81XWH-14-T-0461. The response deadline is September 8, 2014.

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