would be recognized as DNA lesions. To fix these lesions, DNA repair complexes are assembled on the targeted sequence, the DNA is repaired. Damage of the intramolecular recombination substrate can then be repaired and detected if resection goes far enough to produce compatible ends on both sides of the cleavage site and then 3' overhangs are ligated leading to the formation of a single active copy of the gene and the loss of all the sequences between the two copies of the gene. In model systems TFOs can inhibit gene expression at the DNA level as well as induce targeted mutagenesis in the model. TFO-induced inhibition of transcription elongation on endogenous targets have been tested on cell cultures with success. However, despite much in vitro success, there has been limited achievement in cellular applications potentially due to target accessibility. TFOs have the potential to silence silence gene by targeting transcription initiation or elongation, arresting at the triplex binding sites, or introducing permanent changes in a target sequence via stimulating a cell's inherent repair pathways. These applications can be relevant in creating cancer therapies that inhibit gene expression at the DNA level. Since aberrant gene expression is a hallmark of cancer, modulating these endogenous genes' expression levels could potentially act as a therapy for multiple cancer types. Synthetic polyamides Synthetic polyamides are a set of small molecules that form specific hydrogen bonds to the minor groove of DNA. They can exert an effect either directly, by binding a regulatory region or transcribed region of a gene to modify transcription, or indirectly, by designed conjugation with another agent that makes alterations around the DNA target site. Structure Specific bases in the minor groove of DNA can be recognized and bound by small synthetic polyamides (SPAs). DNA-binding SPAs have been engineered to contain three polyamide amino acid components: hydroxypyrrole (Hp), imidazole (Im), and pyrrole (Py). Chains of these amino acids loop back on themselves in a hairpin structure. The amino acids on either side of the hairpin form a pair which can specifically recognize both sides of a Watson-Crick base pair. This occurs through hydrogen bonding within the minor groove of DNA. The amide pairs Py/Im, Py/Hp, Hp/Py, and Im/Py recognize the Watson-Crick base pairs C-G, A-T, T-A, and G-C, respectively (Table 1). See figure for a graphical representation of 5'-GTAC-3' recognition by a SPA. SPAs have low toxicity, but have not yet