Slow Off-rate modified aptamer arrays for biomarker discovery and diagnostic applications

Abstract

DNA microarrays are currently playing a central role in biomarker discovery and in the development of diagnostics for personalized medicine. Our vision is a technology that enables proteomics in the same revolutionary way that DNA microarrays enabled nucleic acid-based omics, allowing simple, reliable, sensitive, accurate, quantitative, and highly multiplexed measurements for the discovery of protein biomarkers and the development of new diagnostics to transform personalized medicine. We recently reached an important milestone, making unbiased protein biomarker discovery routine and fast. Microarrays played a prominent role in our experiments and will be central to the ongoing evolution of our platform. Our technology is powered by a new class of single-stranded DNA-based protein affinity binding reagents we call SOMAmers-slow off-rate modified aptamers. SOMAmers have a dual nature that is essential in our work: under normal conditions (e.g., physiologic in serum), SOMAmers fold into specific shapes that bind target proteins with high affinity (sub-nM K d), but when SOMAmers are denatured, they can be detected and quantified by hybridizing to a standard DNA microarray.