Scalable High Quality Aptamer Generation via Chemically-Augmented Particle Display

ABSTRACTNucleic acid aptamers have shown great promise as the synthetic alternative to monoclonal antibodiesmAbsin therapeuticsdiagnosticsand Randamp D toolsDespite their key advantages of chemical and thermal stabilityconsistent qualitysequenceability and amplifiabilityaptamers are used far less widely than mAbsprimarily due to poor performance in real life applicationsThe root of the aptamer performance problem lies in the limited chemical diversity offered by thenatural nucleic acid basesin contrast to thedifferent amino acids composing antibodyFortunatelyas a synthetic scaffoldaptamers have the potential to incorporate a broad range of chemical diversity through use of modified nucleotidesHoweverdue to fundamental limitations of selection based discovery methodsSELEXchemically modified aptamers are just beginning to scratch the surfaceand have been largely limited to a single type of modificationdeoxyuracil carrying hydrophobic functional groupsThe potential of a broad range of modified bases for aptamer discovery and application is yet unchartedWe propose to develop Chemically Augmented Particle DisplayCAPDa novel approach that enables us to discover modified aptamers with a broad range of chemical diversity that exhibit greatly improved affinityspecificitystability in biological media and the capability serve as a viable alternative to antibodies in real world applicationsOur method has the potential to screen a wide range of distinct chemically modified aptamer librarieswherein we measure the affinity and specificity of every aptamer candidate and explicitly isolate the highest performance binders with the best chemical modificationsIn phase Iwe will develop the CAPD platform and validate aptamers generated with it in standard ELISA assays in serum and compare to natural DNA aptamers and commercial mAbsIn phase IIwe will then develop a production pipeline to create and validate an initial catalog of aptamer pairs to address unmet needs in the research and diagnostics marketsWe will deliver aptamer pairs for no less thanpriority targetsidentified by our customers and healthcare stakeholdersfor use in point of care diagnostics and research assays as which are severely underserved by antibodiesWe will make all these aptamers immediately available for research and diagnostics marketsIf successfulwe believe CAPD will revolutionize aptamer discoveryand enable synthetic aptamers to achieve mainstream adoption in biomedical researchdiagnostics and therapeutics NARRATIVE The purpose of this project is to develop a high throughput quantitative screening platformChemically Augmented Particle Displaythat can rapidly generate a new class of affinity reagents that are fundamental to researchand diagnostic applications by targeting specific biological molecules within complex biological samplesThe affinity reagents generated via Chemically Augmented Particle Displaymodified aptamersexploit a wide range of nonnatural nucleotides and enable unprecedented aptamer performance that is comparable or superior to antibodies while offeringlower costhigh consistency and thermal stabilityWe believe our modified aptamers offer great promise as a superior synthetic alternative to monoclonal antibodies