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Short oligonucleotide sequences can be applied in medicine to sequency specifically target DNA. One type of therapeutic is called a triplex-forming oligonucleotide (TFO; shown below) and these probes can be chemically modified with fluorophores (F) and specific drug molecules (D) that react with the nucleic acid target. Using this principle: i. Describe how TFOs sequence specifically bind with target genes. (10 marks) ii. Discuss chemical modification strategies used to couple DNA reactive small molecules (e.g. cisplatin) to TFOs, and discuss the potential advantages of coupling adjacent fluorophores to these TFOs. (15 marks) ii. Discuss the possible challenges of using TFOs in vivo. (5 marks) Triplex-Forming Oligonucleotide (TFO) Target gene DNA triplex