SOMAmer reagents and the SomaScan platform: Chemically modified aptamers and their applications in therapeutics, diagnostics, and proteomics

The dual nature of nucleic acid aptamers to bind a cognate target or hybridization probe imbue them with a unique advantage for use as reversible pharmaceuticals and reagents to interrogate the proteome. This chapter traces the development of aptamers from discovery to application in therapeutics and diagnostics, with a major focus on the SomaScan Assay, an aptamer-based proteomics platform capable of simultaneously measuring the relative abundance of thousands of proteins in a biological sample. A key to this proteomics solution was the development of slow off-rate modified aptamers, or SOMAmer reagents, which greatly increased the likelihood of obtaining a high-affinity ligand to a given target protein. The mechanisms of protein binding and specificity of these chemically modified single-stranded DNA reagents are explored and the utility of the SomaScan Assay is demonstrated through discussion of key studies and a comprehensive list of 390 published applications of the platform.