Evolution of an Expanded Genetic Alphabet

PICS model

The 'genetic alphabet' is composed of four letters (G, C, A, and T) which form two base pairs as a result of specific hydrogen bonding patterns. We are interested in expanding the genetic alphabet by developing a third base pair composed of unnatural nucleobases, as well as a DNA polymerase to efficiently catalyze the synthesis of DNA containing three base pairs with high fidelity. We have been exploring hydrophobicity, as opposed to hydrogen bonding, to control base pairing. Several unnatural base pairs have been developed which pair stably and selectively in DNA, and are also synthesized with high fidelity by DNA polymerases. We are developing phage display methods for the in vitro evolution of DNA polymerases capable of efficient synthesis of DNA that contains the unnatural base pairs. Use the links below to learn more about the project.