Genetic Alphabet Expansion by Unnatural Base Pair Creation and Its Application to High-Affinity DNA Aptamers

Abstract

Half a century ago, Alexander Rich proposed a genetic alphabet expansion system by the creation of an artificial extra base pair, known as an unnatural base pair. Now, as an ultimate modification technology, the development of unnatural base pairs and their applications has rapidly advanced. Introducing new components into nucleic acids could increase their functionality and moreover create new types of functional molecules. Three types of unnatural base pairs have been shown to function as a third base pair in replication and transcription. By using the unnatural base pairs, high-affinity DNA aptamers that specifically bind to target proteins and cells have been generated. Furthermore, bacteria bearing an unnatural base pair in their plasmids have been created. Here, we introduce a series of unnatural base pairs that function in replication and transcription, as well as their application to DNA aptamer generation targeting specific proteins.