Not listed SBIR PHASE I: OPTIMIZING ASSEMBLY OF BISPECIFIC APTAMER THERAPEUTICS -THE BROADER IMPACT/COMMERCIAL POTENTIAL OF THIS SMALL BUSINESS INNOVATION RESEARCH (SBIR) PHASE I PROJECT IS TO REDUCE THE IMPACT OF PREVENTABLE VISION LOSS CAUSED BY RETINAL DISEASES SUCH AS THE WET FORM OF ADVANCED MACULAR DEGENERATION (WAMD) AND DIABETIC MACULAR EDEMA (DME). VISION LOSS HAS A SIGNIFICANT IMPACT ON THE LIVES OF THOSE WHO EXPERIENCE IT AS WELL AS ON SOCIETY AS A WHOLE. THE RETINAL THERAPEUTICS MARKET WAS $13 B IN 2018 AND IS PROJECTED TO GROW TO $28B IN 2025. THE PROPOSED PROJECT DEVELOPS A NEW TECHNOLOGY TO ADDRESS MULTIPLE ASPECTS OF EYE DISEASE, WHICH IS EXPECTED TO IMPROVE CLINICAL OUTCOMES AT REDUCED COST. THIS SMALL BUSINESS INNOVATION RESEARCH (SBIR) PHASE I PROJECT WILL IDENTIFY THE BEST APPROACH TO COMBINING ANTI-VEGF AND ANTI-IL8 APTAMERS TO GENERATE A BISPECIFIC APTAMER. TWO DIFFERENT APPROACHES WILL BE EVALUATED: 1) DIRECT CHEMICAL SYNTHESIS, IN WHICH THE INDIVIDUAL APTAMER COMPONENTS ARE USED TO FORM A BISPECIFIC APTAMER SYNTHESIZED AS A SINGLE COMPOUND, AND 2) ASSEMBLY BY HYBRIDIZATION, IN WHICH INDIVIDUAL APTAMER COMPONENTS ARE SYNTHESIZED SEPARATELY WITH COMPLEMENTARY EXTENSIONS SUBSEQUENTLY USED FOR ASSEMBLY. THIS PROJECT WILL ASSESS THE EFFECT OF LINKER IDENTITY AND LENGTH ON FUNCTION, AS WELL AS THE INHIBITORY ACTIVITY, WHICH WILL BE COMPARED WITH THAT OF THE INDIVIDUAL APTAMER COMPONENTS. THE BEST PERFORMING BISPECIFIC APTAMERS WILL BE PEGYLATED USING AT LEAST TWO DIFFERENT PEG VARIANTS, AND FURTHER EVALUATED. THE BIOPHYSICAL PROPERTIES OF THE PEGYLATED COMPOUNDS WILL BE ASSESSED. THESE PROPERTIES ARE KEY TO ESTABLISHING PARAMETERS FOR BISPECIFIC APTAMER FORMULATION AND PREDICTING INTRAVITREAL HALF-LIFE. THE BEST PERFORMING PEGYLATED BISPECIFIC APTAMER FUNCTION WILL BE EVALUATED IN VIVO, TO CONFIRM ITS ABILITY TO ENGAGE ITS TARGETS IN AN ESTABLISHED ANIMAL MODEL OF RETINAL DISEASE. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA. $0 11/3/22 Not listed SBIR PHASE I: OPTIMIZING ASSEMBLY OF BISPECIFIC APTAMER THERAPEUTICS -THE BROADER IMPACT/COMMERCIAL POTENTIAL OF THIS SMALL BUSINESS INNOVATION RESEARCH (SBIR) PHASE I PROJECT IS TO REDUCE THE IMPACT OF PREVENTABLE VISION LOSS CAUSED BY RETINAL DISEASES SUCH AS THE WET FORM OF ADVANCED MACULAR DEGENERATION (WAMD) AND DIABETIC MACULAR EDEMA (DME). VISION LOSS HAS A SIGNIFICANT IMPACT ON THE LIVES OF THOSE WHO EXPERIENCE IT AS WELL AS ON SOCIETY AS A WHOLE. THE RETINAL THERAPEUTICS MARKET WAS $13 B IN 2018 AND IS PROJECTED TO GROW TO $28B IN 2025. THE PROPOSED PROJECT DEVELOPS A NEW TECHNOLOGY TO ADDRESS MULTIPLE ASPECTS OF EYE DISEASE, WHICH IS EXPECTED TO IMPROVE CLINICAL OUTCOMES AT REDUCED COST. THIS SMALL BUSINESS INNOVATION RESEARCH (SBIR) PHASE I PROJECT WILL IDENTIFY THE BEST APPROACH TO COMBINING ANTI-VEGF AND ANTI-IL8 APTAMERS TO GENERATE A BISPECIFIC APTAMER. TWO DIFFERENT APPROACHES WILL BE EVALUATED: 1) DIRECT CHEMICAL SYNTHESIS, IN WHICH THE INDIVIDUAL APTAMER COMPONENTS ARE USED TO FORM A BISPECIFIC APTAMER SYNTHESIZED AS A SINGLE COMPOUND, AND 2) ASSEMBLY BY HYBRIDIZATION, IN WHICH INDIVIDUAL APTAMER COMPONENTS ARE SYNTHESIZED SEPARATELY WITH COMPLEMENTARY EXTENSIONS SUBSEQUENTLY USED FOR ASSEMBLY. THIS PROJECT WILL ASSESS THE EFFECT OF LINKER IDENTITY AND LENGTH ON FUNCTION, AS WELL AS THE INHIBITORY ACTIVITY, WHICH WILL BE COMPARED WITH THAT OF THE INDIVIDUAL APTAMER COMPONENTS. THE BEST PERFORMING BISPECIFIC APTAMERS WILL BE PEGYLATED USING AT LEAST TWO DIFFERENT PEG VARIANTS, AND FURTHER EVALUATED. THE BIOPHYSICAL PROPERTIES OF THE PEGYLATED COMPOUNDS WILL BE ASSESSED. THESE PROPERTIES ARE KEY TO ESTABLISHING PARAMETERS FOR BISPECIFIC APTAMER FORMULATION AND PREDICTING INTRAVITREAL HALF-LIFE. THE BEST PERFORMING PEGYLATED BISPECIFIC APTAMER FUNCTION WILL BE EVALUATED IN VIVO, TO CONFIRM ITS ABILITY TO ENGAGE ITS TARGETS IN AN ESTABLISHED ANIMAL MODEL OF RETINAL DISEASE. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA. $0 10/24/22 Not listed SBIR PHASE I: OPTIMIZING ASSEMBLY OF BISPECIFIC APTAMER THERAPEUTICS $256.0k 7/20/21