Abstract
Recent innovations in cutting-edge sequencing platforms have allowed the rapid identification of genes associated with communicable, noncommunicable and rare diseases. Exploitation of this collected biological information has facilitated the development of nonviral gene therapy strategies and the design of several proteins capable of editing specific DNA sequences for disease control. Small molecule-based targeted therapeutic approaches have gained increasing attention because of their suggested clinical benefits, ease of control and lower costs. Pyrrole-imidazole polyamides (PIPs) are a major class of DNA minor groove-binding small molecules that can be predesigned to recognize specific DNA sequences. This programmability of PIPs allows the on-demand design of artificial genetic switches and fluorescent probes. In this review, we detail the progress in the development of PIP-based designer ligands and their prospects as advanced DNA-based small-molecule drugs for therapeutic gene modulation.
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