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Shining a Light on DNA Aptamer Discovery
As a recognition-based macromolecular material, DNA presents advantageous composition structure-property relationships. DNA aptamers can, in principle, achieve target binding specificity and affinity comparable to antibodies; however, their discovery remains slow and labor-intensive. The traditional aptamer discovery or screening platform called Systematic Evolution of Ligands by Exponential Enrichment (SELEX) typically relies on employing a random sequence library to undergo repeated cycles of target binding; harsh elution conditions to dissociate oligonucleotide target complexes; and oligonucleotide amplification to continuously enrich the candidate population with “winners” from prior screening cycles. To address limitations in evolution-based aptamer screening, the Milam group developed an alternative, competition-driven aptamer screening platform called Competition-Enhanced Ligand Selection (CompELS) using designer libraries and gentler enzyme-based DNA elution. To elucidate key parameters governing selection outcomes, the effects of evolution-based vs. competition-driven screening strategies and library design were evaluated in separate parallel aptamer selection studies using a model protein target called mCherry. These results successfully demonstrated a streamlined aptamer selection methodology that accelerates aptamer discovery by integrating CompELS, rational library design, and enzymatic elution.
Bio: Valeria Tohver Milam received her B.S. in Materials Science and Engineering with Honors from the University of Florida. She specialized in metallurgy and also received a minor in Portuguese. For her doctoral studies at the University of Illinois, Urbana-Champaign, she explored the phase behavior, structure and properties of nanoparticle-microsphere suspensions and reported a novel colloidal stabilization mechanism called nanoparticle “haloing.” Her postdoctoral work at the University of Pennsylvania focused on DNA-mediated colloidal assembly. She joined the faculty at the Georgia Institute of Technology in July 2004 as an assistant professor in the School of Materials Science & Engineering and was promoted to associate professor in July 2011. At Georgia Tech her research efforts have focused on oligonucleotides as enabling macromolecular materials and probes in isothermal colloidal assembly-disassembly schemes and high throughput oligonucleotide detection. Her more recent efforts explore DNA as biomimetic ligands that bind in a specific and strong, yet noncovalent manner to non nucleotide targets. Her honors include a Georgia Cancer Coalition Distinguished Scholar Award, CETL/BP Teaching Award, AFRL Summer Faculty Fellowship, 3M Nontenured Faculty Award, NSF CAREER Award, MSE Faculty Fellowship, and NSF Mid-Career Advancement Award.
