Receptors, Ligands, and Catalysts on Demand using Expanded Genetic Alphabets

ABSTRACTTechnology to deliveron demandmolecules that bind targets or catalyze reactions of choice has been a goal of chemistry foryearsEven todaytheory is inadequate to support de novo design of receptors having useful affinity or catalysts having useful turnoverThusmany have sought to create those catalysts on a DNA or RNAcollectivelyxNAusing the Darwinism to these biomolecules to evolveunder laboratory selection pressurethose aptamers and xNAzymesUnfortunatelybecause xNA is built from only four building blocks that carry few functional groupslaboratory in vitro evolutionLIVEhas provided few practical success storiesFirebird scientists createdyears agoan innovative and profoundly disruptive approach to thisWe changed the structure of xNAto give it higher information densityless ambiguous foldsand moieties that confer the functional power of proteinsWe now apply LIVE to artificially expanded genetic information systemsAEGISFigusing chemical theory forcoarse designand laboratory Darwinism forfine tuningtheory cannot dofine tuningand Darwinism cannot docoarse designCommercializedwe have now delivered five AEGIS LIVE productsThese have supported our hypothesisby increasing the information density and functional group diversity of xNA librariesAEGIS libraries will deliver functional xNA molecules more robustly than standard librariesand this improvement will allow aptamers created by AEGIS LIVE to compete with antibodiesespecially in prescribed nichesand to compete with all technologies to generate catalystsOur progress has attracted the Department of Defense as our next customerThe DoD is contracting Firebird to use AEGIS LIVE to create aptamers to bind and detect antibiotics in blood samples to personalize treatment of patients being administered these drugsThis is an example of one of our two overlapping business modelsaA custom research and or collaboration modelwhere Firebird provides AEGIS LIVE as a fee for service to generate receptorsligandsand catalysts chosen by customers and clientsbA product generation modelwhere Firebird uses AEGIS LIVE to generate receptorsligandsand catalysts of its own choosingas commercial products in their own rightThis Phaseproject will develop more case studies to illustrate the intrinsic advantages of AEGIS LIVE aptamers over antibodiesand to provide counter examples to the view that no matter how many more building blocks or functional groups AEGIS hasAEGIS aptamers can never gain any significant share of the$billion market enjoyed by antibodiesor be used in vivoIn addition to generating more aptamersbuilding signaling moieties on to themand benchmarking their performance in blood and other biological fluidsthe academic commercial team joining ScrippsFfAMEand Firebird will expand AEGIS LIVE to create catalysts on demandspecificallysequence specific proteaseslong aholy grailfor catalyst designersThese too will be tested in biological fluids to determine their limits in environments with many other proteins