Triplex forming oligonucleotides (TFOs) have gained significant attention as a potential therapeutic agent to target gene expression.TFOs are a class of DNA oligonucleotides that are capable of binding to the major groove of duplex DNA forming a triple helix. The formation of a triplex along the major groove competes with the binding of transcription factors and other proteins necessary for transcription. Importantly TFOs provide sequence specificity and can be used to target and inhibit expression of specific genes that are associated with a disease state. Furthermore TFOs can also be used as a diagnostic tool for identification of foreign DNA (bacterial or viral) or disease associated mutations.Researchers at the University of Nebraska Medical Center have created a set of novel monomeric heterocyclic bases that are quinoline or quinazoline based structures. These synthetic bases are capable of forming hydrogen bonds with interstrand purine-pyrmidine base pairs and assembling into defined oligomers that have the ability to bind to specific sequences of DNA.In contrast to other triple helix motifs, these novel bases do not require homogeneous stretches of purine or pyrimidine nucleotides to be used as targets, allowing them to be targeted to any known DNA or RNA sequences.