Creation of Unnatural Base Pair Systems Toward New DNA/RNA Biotechnologies

Abstract

The formation of A–T (U) and G–C base pairs is the fundamental rule of genetic information flow in the central dogma of living organisms on Earth. By the same token, the present genetic recombinant biotechnology relies on this base pair complementarity, but the use of only two types of base pairs restricts further technological advancement. Thus, the expansion of the genetic alphabet of DNA, using an artificial third base pair (unnatural base pair), has the potential to open the door to new biotechnologies. Polymerase reactions mediated by an unnatural base pair could site specifically incorporate extra functional components of interest within nucleic acids. To pursue this possibility, researchers have sought to create unnatural base pairs that function as a third base pair, along with the natural base pairs, in polymerase reactions. Recently, several unnatural base pairs with high efficiency and selectivity in in vitro replication and transcription have been created. Here, we describe the recent advancements in unnatural base pair development, focusing on our studies and applications to DNA aptamer selection.