Thioaptamers for Therapeutic Targeting of Pathogenic Human Proteomes
Final rept. 7 Mar 2001-31 May 2005
TEXAS UNIV MEDICAL BRANCH AT GALVESTON
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The objective was to develop novel thioaptamers targeting NF-appaBRef proteins and other relevant proteins, allowing one to modulate the immune response to a BW attack. Combinatorial selection and structure-based design methods were used to develop thioaptamers to bind key proteins in response to pathogens such as hemorrhagic fever viruses and West Nile encephalitis virus. Two lead thioaptamers have been developed and tested against several viral animal models. XBY-6 bound p50 homo- or heterodimer of NF-appaB, AP-1 transcription factors. XBY-6 in liposomes prolonged the incubation period of guinea pigs infected with P18 virulent Pichinde arenavirus, however by 3 weeks nearly all animals were dead despite the treatment while XBY-S2 protected up to 80 of the animals from death. XBY-6 and XBY-S2 also both protected mice that were later infected with West Nile virus. Other thioaptamers were selected from in vitro aptamer libraries to bind additional NF-appaB dimers, TGF-Beta and various flavivirus envelope protein domain III proteins. In addition libraries of thioaptamers were synthesized on beads, one thioaptamer-one bead as well as library of libraries. The beads, when reacted with specific proteins, and the thioaptamers binding specific proteins were selected by flow cytometry.
- Medicine and Medical Research
- Chemical, Biological and Radiological Warfare