DNA Aptamers for Passive Immunity Against Bunyaviruses

Aptamers are oligonucleotides that bind like antibodies to envelope and other viral proteins to block or inhibit viral host cell entry and replication for passive immunity until a patient can mount an effective immune response. In Phase I, Nanohmics proposes to test existing DNA aptamers against Crimean Congo Hemorrhagic Fever envelope epitopes funded by a previous SBIR Phase II contract W81XWH-09-C-0029 and published by the P.I. (BMC Research Notes 5:633, 2012) in tissue culture plaque inhibition assays at the BSL-4 laboratories of the Texas Biomedical Research Institute (TBRI) in nearby San Antonio, TX. The extant CCHF aptamers will also be tested against other Bunyaviruses for plaque inhibition to determine the breadth of efficacy. In Phase II, the CCHF aptamers will be tested in animal models and new aptamers against other Bunyaviruses will be developed and tested as oral formulations in chitin nanoparticles and injectable aptamer-3’-PEG or –Fc conjugates for extended pharmacokinetics in vivo. Nanohmics will also characterize aptamer binding to each viral epitope with 3D computer docking models developed and published by the P.I. (Bruno, J. Molec. Recognition Aug 16:e2809, 2019) to further improve binding, if necessary, by targeted insertion of exotic bases or chemical adducts in the aptamers.