In vitro selection with artificial expanded genetic information systems

TLDR

Designing binders is crucial for many chemicals, but natural DNA/RNA limited to four nucleotides often yields poor binders, motivating the use of expanded genetic systems. The authors performed systematic evolution of ligands by exponential enrichment (SELEX) on libraries of artificially expanded genetic information systems (AEGIS), enabling PCR amplification and cloning of diverse nucleic‑acid binders. This first SELEX using AEGIS produced a nucleic‑acid molecule that binds specifically to cancer cells.

Abstract

Significance Many chemicals are valuable because they bind to other molecules. Chemical theory cannot directly design “binders.” However, we might recreate in the laboratory the Darwinian processes that nature uses to create binders. This in vitro evolution uses nucleic acids as binders, libraries of DNA/RNA to survive a selection challenge before they can have “children” (systematic evolution of ligands by exponential enrichment, SELEX). Unfortunately, with only four nucleotides, natural DNA/RNA often yields only poor binders, perhaps because they are built from only four building blocks. Synthetic biology has increased the number of DNA/RNA building blocks, with tools to sequence, PCR amplify, and clone artificially expanded genetic information systems (AEGISs). We report here the first example of a SELEX using AEGIS, producing a molecule that binds to cancer cells.