Catalytic Aptazymes for Robust OP Nerve Agent Protection

Nanohmics proposes an alternative to expensive recombinant human butyrylcholinesterase scavengers that only stoichiometrically protect military and civilian personnel from about 2 lethal doses of OP nerve agents.  The much less expensive, but potentially more effective, enzymatic alternative is based on an extant published (PMIDs 18224427 and 19051203) high affinity methylphosphonic acid (MPA) OP nerve agent core-binding DNA aptamer sequence (TTTAGT) discovered by the proposed P.I. with previous SBIR funding. Nanohmics will convert this DNA oligo scaffold into a catabolic phosphatase “aptazyme” by incorporation of specific amino acids from natural cysteine-binding phosphatases (CBPs) or exotic nucleotides with the same functional groups as the amino acids. The molecular design and engineering of the aptazymes will be assisted and guided by 3-D aptamer-ligand docking models from the literature (PMIDs 31418487 and 36430888).  Families of these modified oligonucleotides will then be tested for phosphatase activity against several OP nerve agent simulants and pesticides by colorimetric or fluorometric assays and the most active aptazyme families will move into Phase 2 structural characterizatrion by HPLC, mass spectral and NMR analyses followed by synthesis optimization and in vitro neuron and animal challenge/protection studies and filing for FDA approval.