DNA-Targeted Metallodrugs: An Untapped Source of Artificial Gene Editing Technology

Nicolò Zuin Fantoni, Tom Brown, Andrew Kellett. ChemBioChem 22 (13), 2184-2205, 2021.


DNA binding metal complexes are synonymous with anticancer drug discovery. Given the array of structural and chemical reactivity properties available through careful design, metal complexes have been directed to bind nucleic acid structures through covalent or noncovalent binding modes. Several recognition modes – including crosslinking, intercalation, and oxidation – are central to the clinical success of broad-spectrum anticancer metallodrugs. However, recent progress in nucleic acid click chemistry coupled with advancement in our understanding of metal complex–nucleic acid interactions has opened up new avenues in genetic engineering and targeted therapies. Several of these applications are enabled by the hybridisation of oligonucleotide or polyamine probes to discrete metal complexes, which facilitate site-specific reactivity at the nucleic acid interface under the guidance of the probe. This Review focuses on recent advancements in hybrid design and, by way of an introduction to this topic, we provide a detailed overview of nucleic acid structures and metal complex–nucleic acid interactions. Our aim is to provide readers with an insight on the rational design of metal complexes with DNA recognition properties and an understanding of how the sequence-specific targeting of these interactions can be achieved for gene engineering applications.