Nucleic Acid Aptamers (NAAs) are a class of molecules with significant potential in developing molecular tools in biomedical applications. Aptamers are selected using a screening method called Systematic Evolution Ligands by EXponential enrichment (SELEX). Recently, a number of SELEX approaches utilizing whole cells to evolve aptamers against cell-surface membrane proteins were introduced. To this end, we reported on a new variant of SELEX termed Ligand-Guided-Selection (LIGS) to identify highly specific aptamers against a predetermined epitope of a cell-surface target. Hallmark of LIGS rooted in the ability of LIGS to exploit the evolutionary selection step in SELEX as a strategy to evolve highly specific aptamers. The iterative process in conventional SELEX is designed to outcompete low-affinity binders through a competitive process whereby high affinity binders move on through the selection process. By introducing a naturally occurring stronger, highly specific bivalent binder, for example, an antibody (Ab) interacting with its cognate epitope, LIGS out-competes specific aptamers from a partially enriched SELEX pool against cells expressing the same epitope. Utilizing LIGS we have selected aptamers against membrane bound IgM (mIgM) expressed on B-cells. Based on the detailed validation studies conducted using one of the aptamers selected using LIGS, we will show that aptamers identified using LIGS can be optimized into higher affinity variants.

Ligand-guided selection (LIGS): A SELEX variant to identify specific aptamers against cell-surface markers

256th National Meeting (2018)

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