Scalable High Quality Aptamer Generation via Chemically Augmented Particle Display

ABSTRACT Nucleic acid aptamers have shown great promise as the synthetic alternative to monoclonal antibodies mAbs in therapeutics diagnostics and Randamp D tools Despite their key advantages of chemical and thermal stability consistent quality sequenceability and amplifiability aptamers are used far less widely than mAbs primarily due to poor performance in real life applications The root of the aptamer performance problem lies in the limited chemical diversity offered by the natural nucleic acid bases in contrast to the different amino acids composing antibody Fortunately as a synthetic scaffold aptamers have the potential to incorporate a broad range of chemical diversity through use of modified nucleotides However due to fundamental limitations of selection based discovery methods SELEX chemically modified aptamers are just beginning to scratch the surface and have been largely limited to a single type of modification deoxyuracil carrying hydrophobic functional groups The potential of a broad range of modified bases for aptamer discovery and application is yet uncharted We propose to develop Chemically Augmented Particle Display CAPD a novel approach that enables us to discover modified aptamers with a broad range of chemical diversity that exhibit greatly improved affinity specificity stability in biological media and the capability serve as a viable alternative to antibodies in real world applications Our method has the potential to screen a wide range of distinct chemically modified aptamer libraries wherein we measure the affinity and specificity of every aptamer candidate and explicitly isolate the highest performance binders with the best chemical modifications In phase I we 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 mAbs In phase II we 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 markets We will deliver aptamer pairs for no less than priority targets identified by our customers and healthcare stakeholders for use in point of care diagnostics and research assays as which are severely underserved by antibodies We will make all these aptamers immediately available for research and diagnostics markets If successful we believe CAPD will revolutionize aptamer discovery and enable synthetic aptamers to achieve mainstream adoption in biomedical research diagnostics and therapeutics NARRATIVE The purpose of this project is to develop a high throughput quantitative screening platform Chemically Augmented Particle Display that can rapidly generate a new class of affinity reagents that are fundamental to research and diagnostic applications by targeting specific biological molecules within complex biological samples The affinity reagents generated via Chemically Augmented Particle Display modified aptamers exploit a wide range of non natural nucleotides and enable unprecedented aptamer performance that is comparable or superior to antibodies while offering lower cost high consistency and thermal stability We believe our modified aptamers offer great promise as a superior synthetic alternative to monoclonal antibodies